Download THE RETINA

THE RETINA
Development of the retina
The eye is externalized portion of the brain .
Formation of the eye begins with lateral outpouchings of the forebrain during the third
week of development .
The development of the optic cup ( optic vesicle ) reaches a stage where the outer layer of
the optic vesicle becomes the retinal pigment epithelium , while the inner layer of the
optic vesicle becomes the multilayered neurosensory retina . anterior extension of both
layers become the double layer ciliary epithelium .
The ocular ventricle is the potential space between the retinal pigment epithelium and the
neurosensory retina.
PIGMENT EPITHELIUM
Is homolog of the epithelium of the choroid plexus of the brain .
The retinal pigment epithelial cells acquire during development tight junctions that form
a barrier between the neurosensory retina and the choriocapillaries .
CELLULAR ORGANIZATION OF THE RETINA
The layers of cell nuclei are as follows :
1- the outer nuclear layer (ONL) , which contains the cell bodies of the
photoreceptors.
2- The inner nuclear layer (INL) , which contains the cell bodies of horizontal
neurons , bipolar neurons , amacrine neurons , displaced ganglion cells and those
of the glial cells of Muller .
3- The ganglion cell layer , which contains the cell bodies of most of the ganglion
cells , displaced amacrine cells and those of the astroglial cells .
Between the ONL and the INL is the outer plexiform layer (OPL)
OPL = synapses of the photoreceptors ,bipolar cells and horizontal cells .
Between the INL and the ganglion cell layer is the inner plexiform layer ( IPL)
IPL= synapses of the bipolar cells , amacrine cells and ganglion cells .
The optic fibers consist of the axons of the ganglion cells and are unmyelinated while
within the retina . these fibers leave the retina at the optic disc going out of the globe
posteriorly as the optic nerve .
In the retina Muller cell processes fill in almost all volumes not occupied by nerve
cells , relatively rare astroglia or blood vessels .
There appear no physical barrier to diffusion of molecules of moderate size from the
vitreous through the retina into the ocular ventricle .
There is no hindrance to electrical current .
BLOOD SUPPLY OF THE RETINA
Blood vessels coming from the optic nerve head supply the inner two thirds of the
retina . the outer one third is supplied by the choroid .
The inner blood –retinal barrier is formed by tight junctions between retinal blood
vessels endothelial cells .
RETINAL NEUROANATOMY AND ITS PHYSIOLOGIC SIGNIFICANCE
The input to the retina is a time-varying two-dimensional display of an image in its
focal plane .
The image consists of patches of illumination varying in shape, intensity and spectral
content . the information input is received by the PHOTORECEPTORS . the output
of the photoreceptors is processed by a variety of subsequent retinal neurons and
finally by the retinal ganglion cells whose axons leave the retina for higher brain
centers .
The information leaving the retina via axons of the ganglion cells represents a small
number of information processing streams parceling certain types of information
contained in the visual input to axons with particular routing . the axons of the
ganglion cells have several principal as well as minor destinations, and the cells are
sometimes classified by their axonal targets .
The retina also has outputs to the outermost layers of the superior colliculus , where
the information directly or indirectly interacts with motor pathways influencing the
extraocular muscles ,visually concerned cerebellar pathways , such as those dealing
with head and neck movements , and with vestibular and auditory centers .
Pretectal region indirectly receives retinal information important for parasympathetic
and sympathetic regulation of the pupil and ciliary muscle .
PHOTORECEPTORS
These cells are rods and cones . their cell bodies lie in the ONL.
They synapse at the OPL.
An elongated part of the cell protrudes toward the RPE and this part is divided to
outer segment and inner segment which are linked by the ciliary stalk .
The ellipsoid ( the apical portion of the inner segment ) is rich of mitochondria .
There are two types of photoreceptors : rods and cones .
Little is understood about how photoreceptor shape affects function .
The outer segments of both rods and cones contain many double membrane discs or
flattened saccules .
The discs are isolated in rods , but in cones they connects to cell membrane .
The discs are of great importance because the visual pigments , which capture the
photons to begin the visual process , appear to be built into the discs .
The visual pigments are insoluble .
They are intrinsic membrane proteins .
They constitute > 50% of the protein of the outer segment .
Visual pigment = aldehyde of vit.A and various proteins .
Outer segments are capable of regeneration .
Destruction may occur on RD , vit.A def.
Surrounding the photoreceptor outer and inner segment a gel termed
interphotoreceptor matrix (IPM) .
Both cone and rod discs shed and are phagocytosed by RPE.
Rods shed shortly after morning
Cones peak shedding at the end of the day.
Outer segment … production and destruction .
RECEPTOR OUTER SEGMENT AND PIGMENT EPITHELIUM RELATIONS
RPE is implicated in the ocular transport of vit.A and it’s derivatives .
The regeneration of visual pigment is one factor in dark adaptation after the
significant bleaching of such pigment .
The RPE contains melanosomes which contain melanin .
The melanosomes minimize the scattering of light from one photoreceptor to another.
Detachment of the retina consists of the physical separation of the retina from its
close approximation to the RPE .
Parameters that contribute to attachment are :
1- factors regulating the volume of fluid in the ocular ventricle .
2- acid mucopolysaccharides , known to be present in the fluid of the ocular
ventricle , which could contribute to its viscosity or to the cohesion of
neighboring membranes .
3- a barb action of the elongated melanosomes in the long microvilli from the RPE .
the RPE also has phagocytic function . the membrane of the outer segment heals over.
The receptor axes are so tipped as to orient them to the exit pupil of the eye rather than to
the center of the ocular sphere . this maximizes the ability of any one photoreceptor to
capture light .
During the act of accommodation orientation of receptor outer segments is altered .
It is now clear that after bleaching of photopigment , the 11-cis-retinaldehyde has
been converted to all-trans-retinaldehyde . there is then a conversion to all-transretinol by a dehydrogenase .
The RPE is the site where reoxidation of retinol to retinal occurs , as well as
reisomerization of the all-trans-isomer to the 11-cis-isomer .
Important carrier proteins are involved in moving these vitamin A derivatives
between the photoreceptors and RPE in both directions .
DISTRIBUTION OF PHOTORECEPTORS AND OTHER NEURONS WITHIN
THE RETINA
How different types of photoreceptors are distributed in retinas .
Regions biased for inspecting details are richer in cones by virtue of containing
thinner cones and more of them per unit area than elsewhere and more ganglion cells
per unit area as well . such a region is termed central region .
Physiologically ,central regions tend to be free of major blood vessels and in certain
retinas even capillaries .
In the human the extent of the cone-rich area is about 5.5mm in diameter, and it tends
to be variably demarked by the presence of yellow , nonphotolabile carotenoids in
photoreceptor axons and some inner retinal cells . the pigment is largely zeaxanthin .
these pigments give the region the name .. macula lutea .
The center of the cone-rich region contains a pit or fovea .
In the human the full depression occupies about 5 degrees of arc or about 1.5mm on
the retina .
In the center of the fovea there is the foveola ( 54 minutes of arc = 260micrometer ).
Here only photoreceptor type present ( cones ).
Cones in this region have the finest diameters of the retinal cones ( 1.5 micrometer )
and this is the region of highest concentration of cones in the retina .
Functionally the fovea is the position of the retina to which , by turning the eye ball ,
a person brings the image of what ever is of greatest psychologic interest in the visual
field .
Anatomically , the retina in the central fovea consists entirely of the outer and inner
segments of the photoreceptors , the photoreceptor cell bodies , and the intervening
glial cell processes .
The axons of the photoreceptors , the so-called Henle fibers , are swept horizontally and
leave the foveal area . the terminals of foveal cones , the horizontal neurons and bipolar
neurons with which they interact , and those amacrine cells and ganglion cells that
receive information from the foveal cones are centrifugally and laterally displaced so
that, in the foveolar region , all these elements are missing , and they are minimized
elsewhere in the fovea .
The foveola is surrounded by a parafoveal region , and this by a perifoveal region .
They are 2.5mm and 5.5mm in diameter respectively .
If one imagines a vertical line passing through the central fovea , thus separating
nasal retina from temporal retina , axons from ganglion cells of the temporal retina
will project to the LGN and superior colliculus on the same side of the brain as the
eye , whereas ganglion cells from the nasal half of the retina will cross in the optic
chiasm and terminate in the LGN and superior colliculus of the contralateral brain .
The adult human retina has about 120 million rods and about 6-7 million cones .
Cone density peaks in the fovea at about 199.000 cones / mm2 , and then falls off
sharply in all directions , although there is some concentration of cones along the
horizontal meridian , particularly in the nasal retina .
The area for useful color vision in humans has a diameter of 9mm centered on the
fovea .
The rod-free center of the fovea may be deficient in blue sensitive cones .
The human rod density peaks in a somewhat elliptical ring .
The highest rod concentration ( 160.000 /mm2 ) along this configuration occurs in the
superior retina .
It is important to realize that when light levels are in the photopic range of cone
function , their activity tends to command all retinal output .
INL contains the somal regions of bipolar neurons and also contains those of
horizontal and amacrine neurons , interplexiform neurons , rare displaced ganglion
cells , and the somal regions of the glial cells of Muller .
In this layer it is difficult to know the exact distribution of cells across the retinal
area.
Situation for the distribution of ganglion cells is somewhat better , because this region
belong only to ganglion cells and displaced amacrines .
However , there are several varieties in ganglion cells in terms of size and distribution
of processes .
It is fair to state that the macular region in the human retina is rich in small ganglion
cells and that, by comparison to concentration of cones in this region , it seems likely
that there are enough small ganglion cells to permit the consideration that each could
receive information via intermediate cells from a rather small population of cones .
A chain of information transmission in which the ratio of receptors connected via
intermediates to ganglion cells approaches 1:1 is what one might idealize for a region
of high detail discrimination .
In other retinal regions there is a high ratio of rods to ganglion cells and , as expected
, a high sensitivity to detecting light but poor form discrimination .
SYNAPTIC CONNECTIONS OF THE RETINA
Receptor terminals are spherules or pedicles .
Spherules are small and round while pedicles are large and have flat bases facing the
rest of the OPL .
Rods end in spherules and cones in pedicles .
Processes of horizontal cells and bipolar neurons are deeply invaginated in rod
spherules but only superficially invaginated into the bases of pedicles .
The receptor terminal is full of synaptic vesicles .
There is some contacts between cones and cones and cones and rods . these contacts
helps in spread of current between cells .
Horizontal cells occur in the outer portion of the INL and are neurons whose
processes are disposed in a manner suggesting a role in the horizontal integration of
retinal activity .
An amacrine cell is a neuron with no morphologically definable axon . there soma lie
in the inner aspect of the INL.
RETINAL SYNAPTIC MECHANISMS AND PUTATIVE CHEMICAL
NEUROTRANSMITTERS
The photoreceptors have terminals rich in synaptic vesicles and evidence strongly
indicates that the transmitter of the photoreceptor is glutamate , an excitatory (
depolarizing ) aminoacid .
Interphotoreceptor contacts between cones , or rods and cones , have frequently been
noted and appear to include gap junctions , indicating the possibility of electronic
interactions between these cells .
RETINAL SYNAPTIC MECHANISMS AND PUTATIVE CHEMICAL
NEUROTRANSMITTERS
The photoreceptors have terminals rich in synaptic vesicles and evidence strongly
indicates that the transmitter of the photoreceptor is glutamate , an excitatory (
depolarizing ) aminoacid .
Interphotoreceptor contacts between cones , or rods and cones , have frequently been
noted and appear to include gap junctions , indicating the possibility of electronic
interactions between these cells .
The action of a neurotransmitter or neuromodulator , promoting excitation or
inhibition , is both a parameter of the nature of the agent and of the membrane
mechanisms determining the response of a particular cell to the agent .
For example , the action of acetylcholine on skeletal muscle is excitatory , but its
action on cardiac muscle is inhibitory .
Finally , when transmitter or neuromodulator are released it is obviously desirable to
terminate their presence by enzyme action or other mechanisms after they have
carried out their signaling function .
Thus the glial cells of Muller appear to take up and metabolize glutamate .
ELECTRICAL ACTIVITY AND INFORMATION PROCESSING BY RETINAL
NEURONES .
The electrical activity of individual cells can be recorded by intracellular electrodes
and sometimes by extracellular electrodes ( animals ) .
Each cell in the chain of nerve cells processing visual information has its own
receptive field .
There is a considerable overlapping of receptive fields of cells near each other in the
retina .
Any receptive field has sometimes distinct regions , such as ( center ) and ( surround
).
When a small spot of light , at an intensity above back ground , is first positioned on
the center and then on the surround , opposite responses are often elicited .
If the spot of light is expanded to stimulate simultaneously both center and surround
diminished or absent response will be elicited .
Spot of darkness also has the same response .
The spatial dimensions of receptive field centers are one determinant of spatial
resolution – the smaller the center the smaller the possible spatial resolution .
Electrodes across the eye ( see ) a summation of the various individual cell responses.
Retina with its population of rods and cones modifies the signals reaching ganglion
cells as a function of its adaptational state , that is to say , when it is dark adapted to a
lower level of illumination or when it is light adapted to a more intense illumination .
Altering the adaptational level involves both photochemical and electrochemical
changes in the receptors and probably at subsequent retinal processing levels .
ALL EVIDENCE POINTS TO A FUNCTIONAL ORGANISATION IN THE
RETINA AND HIGHER VISUAL SYSTEM THAT IS RELATIVISTIC AND
DIRECTED AT DISCERNING LOCAL CONTRASTS THAT ESTABLISH
BORDERS BETWEEN AREAL ELEMENTS IN THE COMPLEX IMAGE OF THE
VISUAL FIELD , RATHER THAN MECHANISMS FOR ASSAYING THE
ABSOLUTE LEVELS OF LIGHT IN LOCAL AREAS .
A retinal locus receiving an image of an area perceived as ( black ) at a high level of
illumination may actually be receiving a greater absolute quantity of light than a
retinal locus receiving an image of an area perceived as ( white ) at a dim illumination
if , in the former instance , the black area is receiving relatively much less light than
its general surround and in the later instance , if the white area is receiving relatively
much more light than its surround .
Moreover , the color perceived to be present in a patch will depend on the nature of
the perceived color in its surround .
NEURAL NETWORK OF VISUAL APPARATUS ARE MORE KEYED TO
DETECTING FLUCTUATIONS IN THE RETINAL IMAGE CAUSED BY
CHANGES IN LOCAL RELATIVE INTENSITY THAN FOR DETECTING
STEADY DISPLAYS.
ONE SOURCE OF THIS FLUCTUATION IS MOVEMENT OF THE IMAGE OF
THE VISUAL FIELD ON THE RETINA .
THE LATTER FACT RAISES AN IMPORTANT POINT REGARDING
MOVEMENTS OF THE EYE .
ONE SOURCE OF THIS FLUCTUATION IS MOVEMENT OF THE IMAGE OF
THE VISUAL FIELD ON THE RETINA .
THE LATTER FACT RAISES AN IMPORTANT POINT REGARDING
MOVEMENTS OF THE EYE .
More over if by some means the image of the visual field is made to hold its position
on the retina despite eye movements , the image fades and is no longer seen by the
observer .
This explains why the shadows of the blood vessels of the retina are not in constant
view in superimposition on the field of vision , because by having a fixed relation to
the retina and the pathway of light , they are adapted out of the perceived image .
The important point therefore is that a normal fine instability of the eye contributes to
the normal visual process .
Photoreceptors hyperpolarize when exposed to flashes of light .
Single rod may be excited by a single quantum of light .
For a single rod to be excited by a single photon represents an exquisite sensitivity .
There is more synaptic activity in the dark .
In the dark a current is flowing into the outer segment from the rest of the
photoreceptor .
The effect of a flash of light is to diminish this dark current . this diminution is
achieved largely by decreasing the conductance for sodium ion across the plasma
membrane of the outer segment .
Light causes a decrease rather than increase in calcium activity in outer segments.
In the dark a low level of calcium ions enters outer segments along with sodium ions.
This entry of calcium ions is countered by the activity of a counterporting mechanism
that exchanges intracellular calcium and potassium for external sodium .
Since in the dark calcium enters the cell along with sodium via the light modulated
channels , and as the exchange mechanism is not regulated by light , when the light
sensitive channel is closed , the continuing operation of the exchange mechanism
decrease intracellular calcium .
The main agent for regulating the channels for entry of sodium is cyclic guanosine
monophosphate (cGMP) .
Photoreceptors are extraordinarily rich in cGMP.
Light causes losses of cGMP by a complex mechanism called the cyclic GMP
cascade , wherein bleached rhodopsin activates a nucleotide-binding protein , and this
intermediate activates a cyclicGMP phosphodiesterase that hydrolyzes cyclic GMP to
GMP .
Studies have shown that cyclic GMP can act on the inner face of the plasma
membrane of the rod outer segment to open conductances .
This effect is suppressed by light .
It is therefore clear that a channel involved in the transduction in rods , and also in
cones , is light sensitive , because appropriate levels of cGMP keep it open in the dark
, while the loss of cGMP through the activation of cGMP phosphodiesterase via the
light initiated cGMP cascade allows the channel to close .
To complete the story , cGMP is regenerated from GTP by the activity of guanylate
cyclase .
Chelating calcium rapidly and massively increased cyclic GMP levels in
photoreceptors , suggesting that this enzyme is inhibited by calcium .
The significance of light insensitive mechanism exchanging calcium and potassium
for sodium is thus seen as a way to promote the resynthesis of cGMP by reducing the
calcium level after light has caused a loss of this cyclic nucleotide .
Both rods and cones hyperpolarize to light flashes , but rods recover more slowly than
do cones from bright flashes presented against a dark background , and rods have a
lower absolute threshold to flashes presented against a dark background .
Horizontal cells only sensitive to light intensity or luminosity are called ( L ) type ,
while those whose polarity is color sensitive are called ( C ) type.
Horizontal cells are often coupled by gap junctions , and their effects often feed back
onto cones , possibly to rods , and possibly feed forward onto bipolars .
Bipolar neurons respond to contrast , not simply light intensity , and these center
versus surround phenomena are also evident at the ganglion cell level .
In the photopic range spatial detail is best detected by brightness contrast rather than
color contrast . the best detectors of brightness contrast are red or green cones , the
relatively sparce blue cones less so.
Brightness contrast is poorly detected by rods operating in the scoptopic range .
The likely anatomic basis for the center of this receptive field is the population of
photoreceptors with which these bipolars are in direct synaptic contact , whereas the
surround may represent another population of photoreceptors by which the bipolars
are indirectly influenced via horizontal neurons .
The visual system contains ( on ) and ( off ) pathways .
Neurons that depolarize in response to an increase in the intensity of light above
background in their receptive field are termed (on ) cells , where as those that
depolarize in response to the offset or diminution of light compared to background
are termed ( off ) cells .
Since the light diminishes the sodium current entering the photoreceptors , all
photoreceptors hyperpolarize in response to increasing light and depolarize to
diminishing light and are therefore ( off ) cells .
Bipolars that depolarize to light are ( on ) cells , whereas those that hyperpolarize to
light are ( off ) cells .
As the latter mimic the polarization responses of photoreceptors , the synapse
between them is said to be ( sign conserving ) .
Conversely , the synapse between photoreceptors and those bipolars that depolarize to
light is termed ( sign inverting ) .
The two bipolar classes may function in detecting relatively bright centers in darker
surrounds , or the converse .
Particular amacrine cells probably serve in abstracting particular environmental
features to permit ganglion cells to respond to such things as movements in particular
directions or to objects of particular sizes, orientations , shapes or patterns .
Ganglion cells :
- ( on ) cells
- ( off ) cells
- ( on-off ) cells
It should be remembered that individual ganglion cells summate the effects of
numerous impinging inputs of electronic or chemical synapses and the location of a
synapse on a cell is also of possible significance .
Ganglion cells largely fall into one of two major groups characterized by whether
their discharge pattern is sustained or phasic .
A ganglion cell exhibiting a sustained discharge is not responsive to the
rearrangement of dark and bright elements in its receptive field provided that the net
illumination is constant , whereas phasic ganglion. cells would respond to each such
change .
Fast-conducting axons from the retina tend to end in the magnocellular layers of the
LGN , whereas axons of medium conduction velocity project to the parvocellular
layers of the LGN .
Receptive fields of the ganglion cells tend to increase with distance from the central
area or fovea .
It should be clear from the preceding discussion that the retina is organized to permit
the lateral interaction of nerve cell networks and that this often can take the form of
lateral inhibition .
To summarize the foregoing discussion , one can consider the retina ( and higher
visual system ) to have parallel depolarizing ( on- center ) and hyperpolarizing ( offcenter ) informational pathways , with a neuron assigned to a pathway by the polarity
of its response to the onset of light on its receptive field .
Opposite effects occur with light offset , and cells that exhibit ( on-off ) behavior are
thought to connect to both information streams .
ROLE OF GLIA
The membrane potential of the Muller cell may reflect its behavior as a potassium
electrode .
Glia undoubtedly have phagocytic functions in pathologic states and certainly
functions that are still unknown .
THE OPTIC NRVE
The optic nerve can be considered to have four portions :
- the intraocular portion .
- intraorbital portion
- intracanalicular portion
- intracranial portion
1 million axons that pass from each eye into the optic nerve conduct partially
processed visual information from the retinal ganglion cells to the lateral geniculate
body, superior colliculus , hypothalamus , and certain midbrain centers .
There are now considered to be two parallel pathways in the anterior visual pathways
carrying different types of visual information .
The luminance pathway , also called M ( for magnocellular ) , utilizes larger retinal
ganglion cells with larger diameter axons that synapse in the magnocellular layers of
the lateral geniculate body .
They are most sensitive to change in luminance at low light levels , subserve motion
perception , and are relatively insensitive to color .
Only a small proportion of all ganglion cells are part of the M pathway .
The color or P ( for parvocellular ) pathway consists of smaller ganglion cells that
project to the parvocellular lateral geniculate layers and preferentially carry
information on color and fine detail .
This group includes the majority of retinal ganglion cells , including the midget cells
of the foveal area .
After passing through the lamina cribrosa to enter the intraorbital portion , the fibers
gain a myelin sheath .
From this point onward the impulse is carried by saltatory conduction typical of white
matter tracts and myelinated peripheral nerves .
Depolarization occurs only at the nodes of Ranvier , with the impulse jumping from
node to node .with this saltatory conduction , the impulse passes along the axon more
rapidly than it would by conduction of an action potential , such as in unmyelinated
fiber .
Saltatory conduction also conserves metabolic energy , because only the exposed
portion of the axon membrane at the node needs to be repolarized , not the entire
length of the axon .
What will happen in demyelinating diseases ??
The number of fibers appear to be related to the size of the optic disc as it is seen
clinically . the larger the optic disc , the more the number of fibers .
There are more than twice the number of axons in a fetal primate eye than in the adult
eye .
It is believed that ganglion cells die if their axons do not successfully synapse with
appropriate targets in the brain .
After birth , this attrition of the optic nerve fibers slows dramatically .
During a 75-year human life , the further loss of ganglion cells , presumably from
aging , encompasses only 25% of the total .
Blacks have larger discs and hence larger cups .
The movement along axons seems to occur by at least two different processes : rapid
axonal transport and slow axoplasmic flow .
Rapid axonal transport is bidirectional , orthograde from the ganglion cell body to the
axon terminal and retrograde from the terminal to the ganglion cell body .
This active transport requires metabolic energy , which is obtained from ATP
produced locally within each axon segment along the way .
200 – 400 mm / day
A variety of chemical messages , hormones and foreign material such as toxins and
viruses can be passengers in this system .
Slow axonal flow can be traced as the movement of soluble proteins synthesized in
the cell body toward the axon terminal at a rate of only 1 to 3 mm / day .
THE GLIA
The predominant glial element in the optic nerve head is the astrocyte .
Their function to support the bundles of nerve fibers as they turn to enter the optic
nerve from the retina
Astrocytes also provide a cohesiveness to neural compartment .
Astroglia in the nerve head presumably also serve to moderate conditions for neural
function , for example , by absorbing excess extracellular potassium ions released by
depolarizing axons and by storing glycogen for use during transient oligemia .
They function in the nerve head like the Muller cells of the retina .
The oligodendrocytes form and maintain the myelin sheaths , as they do elsewhere in
the CNS .
THE BLOOD VESSELS
The optic nerve microvascular bed resembles anatomically the retinal and CNS
vessels .
The optic nerve vessels share with those of the retina ( and of the CNS in general )the
physiologic properties of autregulation and the presence of the blood brain barrier .
Because of autoregulation , the rate of blood flow in the optic nerve is not much
affected by intraocular pressure ( IOP ) .
In the retina and optic nerve , as in the brain , the vascular tone is increased by
autoregulation when blood pressure rises , increasing the resistance to flow , so that
the flow level is not affected by the elevated blood pressure .
Elevated IOP compresses the vein , increasing the total resistance to flow through the
arteriovenous circuit , which would reduce the blood flow for a given of arterial
blood pressure .
However , autoregulation compensates for venous compression by reducing the
vascular tone in other parts of the circuit as IOP rises , so that blood flow is
maintained despite the venous compression caused by intraocular pressure .
Autoregulation seems to be accomplished in part as a response to the degree of
arterial stretching and in part as metabolic autoregulation … as carbon dioxide
concentration , pH , or oxygen level .
CO2 is a particularly powerful vasodilator . CO2 accumulates because of inadequate
blood flow , the vessels dilate and the blood flow increases .
PAPILLEDEMA ( OPTIC NERVE-HEAD SWELLING )
A variety of intracranial conditions may result in papilledema .
Obstruction of cerebrospinal fluid exit , which results in an elevated intracranial (
hydrostatic pressure .
Subarachnoid space extends through the optic canal around the optic nerve and the
hydrostatic pressure is transmittied there around the optic nerve .
The central retinal vein , as it crosses the nerve sheaths in the mid-orbit is subject to
external compression by the subarachnoid pressure .
When the subarachnoid pressure exceeds venous pressure , compression of the vein
increases resistance to flow at that point and elevates slightly the venous pressure
upstream .
If spontaneous venous pulsations are present in the optic disc , as happens in many
normal individuals , they disappear when the elevated central retinal venous pressure
exceeds the normal IOP .
It is now thought that the main pathophysiologic event is an impairment of slow
axoplasmic flow . the tissue pressure of the axons within the eyes is equal to IOP ,
whereas in the orbit the intra-axonal tissue pressure is governed by the subarachnoid
pressure .
the lamina cribrosa is the partition that separates the two pressure compartments ,
where axons are subjected to this pressure gradient .
under normal conditions the IOP is greater than the subarachnoid pressure and the
gradient may be thought of as augmenting the movement of axoplasm out of the eye .
however , when intracranial pressure equals or exceeds IOP , the forces of slow
axoplasmic flow encounter a diminished or reverse pressure gradient . the axons in
the optic nerve head become distended .
although slow axoplasmic flow is impaired , the axons often continue to function .
visual function may be quite normal in chronic papilledema for a long time , except
that the physiologic blind spot is enlarged when the swollen disc displaces the inner
retina next to the optic nerve head .
Not all swellings of the optic nerve head are papilledema due to increased
subarachnoid pressure .
For example : anterior ischemic optic neuropathy in which the nerve head swells is
most likely an infarction of the anterior optic nerve .
Other swellings may occur as a result of neoplastic infiltration , acute glaucoma , and
hereditary neuropathy .
OPTIC ATROPHY
Nonglaucomatous optic atrophy is characterized by a loss of axons ( and their retinal
ganglion cells ) in response to lethal insult to the cell .
With loss of its substance , the optic disc flattens and turns pale .
Localized insults , which occur most often in the anterior optic nerve and retina ,
injure bundles of axons and in the visual field produce scotomas and other visual field
defects that are shaped like the course of nerve fiber bundles .
Lesions of the posterior optic nerve also can rarely injure bundles of axons and
produce nerve fiber bundle defects . the usual compressive lesion in this location
almost always has a diffuse effect or affects preferentially the small diameter macular
fibers , resulting in a central scotoma .
Whichever the underlying etiology of optic atrophy , the integrity of the axon is
interrupted anatomically or physiologically at some point in its course .
The proximal segment of the axon , being disconnected from its ganglion cell ,
promptly degenerates . it is no longer receives support through the orthograde axonal
transport mechanism .
There remain the ganglion cell and the attached fragment of axon that extends from
the ganglion cell to the cite of injury .
It has been shown that mammalian optic nerve fibers cannot only regenerate , but
reestablish connections with their target sites in the central nervous system if
provided with a segment of peripheral nerve tissue as a bridge within which to grow .
When atrophy occurs , the astroglia migrate into the spaces vacated by the
degenerated axons . blood vessels are reduced in number but remain in proportion to
the glial and neuronal tissue that persists and requires nutrition .
When optic atrophy occurs , the typically red color of the optic disc rim becomes pale
.
COLOR VISION
Color is purely a sensory phenomenon and not a physical attribute .
Human awareness of color arises out of subjective visual experiences in which given
sensations are ascribed names .
Agreement between individuals in color naming derives from a tacit acceptance that
given sensations can be reliably described with color names .
The perception of color varies complexly as a function of multiple parameters ,
including the spectral composition of light coming from the object , the spectral
composition of light emanating from surrounding objects , and the state of light
adaptation in the subject just prior to viewing any given object .
A remarkable and as yet not completely understood phenomenon that is characteristic
of color vision is that of color constancy .
Color constancy refers to the phenomenon in which the apparent color of an object
does not seem to vary appreciably when the wavelengths and intensity of light
illuminating the object are altered .
Color constancy appears to be related to a phenomenon in which :
1- colors acquire their appearance primarily by relative comparisons to other objects
in their immediate vicinity and
2- these comparisons change only minimally with broad changes in spectral mixtures
of light falling on scenes .
COLOR AND VISIBLE SPECTRUM
The rainbow of hues visible in the solar spectrum was first reported by Sir Issac
Newton , who correctly supposed that individual components of the spectral mixture
were in some way related to differential stimulation of photoreceptor units in the eye ,
providing the basis for the physical stimulus evoking color sensation .
If a prism is placed in the path of a narrow beam of sunlight , the path of the light
beam will be refracted or bent toward the base of the prism .
Short wavelengths are bent to a greater extent than are long wavelengths.
The index of refraction for an optical medium differs according to wavelength .
This variable extent of refraction spreads a polychromatic white beam of light into its
component wavelengths , a phenomenon referred to as spectral dispersion .
The array of individual wavelengths thus exposed is referred to as the visible
spectrum .
The sensations that these individual wavelengths evoke are called the spectral colors.
Violet light at a wavelength of 430 nm, blue light of 460nm , green light of 520nm ,
yellow light of approximately 575nm, orange light of 600nm , and red light of
650nm.
Wavelengths falling between these values produce color sensations that are often
given compound names , such as blue-green or yellow – green .
Remember , though, that such stimuli remain monochromatic , and the sensations
they evoke depend on much more than just wavelength and intensity .
The color a given stimulus evokes depends critically on the context within which it is
seen, a phenomenon called simultaneous color contrast .
As will be shown later , color is neural encoded in the afferent visual system by cells
whose receptive fields are tuned to the detection of simultaneous color contrasts .
THE TRICHROMATIC THEORY OF HUMAN COLOR VISION
Two major theories to explain the properties of human color vision .
These two principal theories are now referred to as the theory of trichromacy ( or the
Young-Helmholtz-Maxwell theory ) and the opponent process theory .
Over the past several decades , it has become apparent that human and nonhuman
primate color vision is indeed mediated by an essentially trichromatic process at the
receptor level , but is encoded for neural transmission in a physiologic paradigm of
the color opponent process .
Studies of individual photoreceptors , allowed the identification of three mutually
exclusive classes of cones in the primate retina having differing , but overlapping ,
spectral sensitivities .
One class of photoreceptors has a spectral sensitivity that peaks at approximately
440nm to 450nm . these receptors , which are more sensitive to the short wavelength
end of the spectrum , are sometimes referred to as short wavelength sensitive
receptors , or blue cones .
A second class of middle wavelength sensitive receptors has a spectral sensitivity that
peaks at between 535and 550 nm , sometimes referred to as green cones .
The third class has a spectral sensitivity peaking at between 570 and 590 nm . these
are referred to as long wavelength sensitive photoreceptors or red cones .
The overlapping of the spectral sensitivities of these three classes of cones means that
no individual class of cones can be stimulated in isolation by any one wavelength .
THE OPPONENT COLOR THEORY
Certain select pairs of colors such as red versus green or yellow versus blue were
found to be mutually exclusive .
Mixing lights of such colors did not yield composite sensations .
For instance , red light and green light mixed together produced an appearance of
yellow , while mixing blue light with yellow light produced an appearance of white .
Thus some colors seems to be mutually exclusive or opponents of one another .
COLOR MIXING , METAMETRIC MATCHES , AND COMPLEMENTARY
WAVELENGTHS .
Helmholtz found that any colored light one wished to use as a reference could be
matched by a suitable mixture of three strategically chosen lights mixed together .
While Helmholtz established the qualitative nature of this relationship , it was later
put on a quantitative basis by Maxwell .
Mixtures of light that produce identical-appearing colors are called metameric
matches .
Mixtures that are physically identical to one another ( have identical spectral
compositions ) are said to be isomeric matches .
Normal observers can always produce metameric matches , but only if at least three
spectral lights are given.
While such metameric matches can be physically very different from one another ( in
terms of their spectral distributions ) , they nonetheless appear to be identical in color
and brightness .
This appearance of sameness is linked to the relative extent to which each of the three
retinal cone classes are excited .
Light mixtures that cause the same proportional stimulation of the three receptors will
result in the same sensation .
In those special cases of metameric matches of light seen as “ white “ , it is often
possible to achieve a match by the proper mixing of only two appropriately chosen
spectral lights .
Such pairs of monochromatic light sources are said to have complementary
wavelengths .
NEURAL ENCODING OF COLOR
The receptive fields of neurons are classified as being color coded , if some aspect of
the cell responses are found to be specific for some color attribute .
For instance , a cell may respond more vigorously to stimulation by light of one
wavelength than of another , or the nature of the response may differ as a function of
wavelength .
Two broadest categories of such cells in the anterior visual system are opponent color
cells and double opponent cells .
OPPONENT COLOR CELLS
Tracing afferent visual pathways beyond the photoreceptors , the first cells found to
have specific color-related properties are the opponent color cells .
Such cells have differing polarity of responses for differing portions of the visible
spectrum .
An example of an opponent color cell is as follows :
Stimulation by yellow light increases the tonic firing rate of such a cell , whereas
stimulation by blue light inhibits or eliminates its rate of firing .
Stimulation by similar-sized spots of white light produces no response .
The latter phenomenon may be explained by presuming that simultaneous white
stimulation of both excitatory and inhibitory components of the cell’s receptive field
will result in a net zero response in firing rate .
Opponency of such cells can be characteristically divided into two large groups :
those having blue-yellow opponency , and those having red-green opponency .
Red-green color opponent cells are tuned to detection of varying levels of stimulation
of middle and long wavelength sensitive cones , and are best suited to the detection of
red-green color contrasting borders .
It is believed that there are also cells that sum the input of red and green cones to
produce a yellow signal .
Blue – yellow opponent cells then detect levels of stimulation of blue cones as
compared to the summed effect of stimulating both red and green cones .
DOUBLE OPPONENT CELLS
Cells that have opponent receptive field properties for both color and space are said to
be double opponent .
Double opponent cells are optimally organized for the detection of simultaneous color
contrast .
The phenomenon of simultaneous color contrast can be demonstrated by viewing
restricted areas surrounded by contrasting color regions .
For instance , a small field of gray surrounded by a field of red will appear to contain
a greenish cast .
Conversely , the same gray spot viewed in any region surrounded by green will
acquire a reddish appearance .
The general rule of simultaneous color contrast is that the color of a restricted region
will tend toward the complementary color of its surround .
Simultaneous color contrast is closely related to the phenomenon of color constancy
referred to previously .
The color that a given light will appear to have depends critically upon closely
adjacent areas with which it is compared and contrasted .
A localized area illuminated by monochromatic light of 585nm wavelength can take
on a variety of seemingly different colors , depending entirely on the areas
surrounding it .
For instance , a spot of 585nm will acquire a green color when embedded in a
surround of 650nm but will appear to be red when surrounded by a field of 540 nm .
When surrounded by a field of identical wavelength but 0.7 log unit brighter , it will
acquire a gray appearance , whereas if the surround of the same wavelength is 2 log
units brighter , the spot will appear to be black .
Again , if the spot of 585nm light is surrounded by a field of somewhat shorter
wavelength , for instance 570nm , but 1 log unit brighter , the spot will appear to be
brown .
RETINAL DISTRIBUTION OF COLOR-SPECIFIC NEURONS
The density of cones in the retina falls sharply outside the fovea , but cones of all
three varieties are present , though in much smaller numbers , all the way to the ora
serrata .
The center of the fovea is unique both in having the highest spatial density of cones
and in having a pure mosaic of red and green cones , with blue cones being
eliminated from the photoreceptor population within the central 1/8 degree of the
visual field .
PECULIARITIES OF THE BLUE CONE SYSTEM
Both visual acuity and contrast sensitivity are poorer in blue light than in red or green
light .
This phenomenon is due not only to the absence of short wavelength sensitive cones
in the foveal center but also to the relative scarcity of blue cones , which are much
fewer in number in all retinal areas than are middle wavelength sensitive or long
wavelength sensitive receptors .
COLOR ENCODING IN THE CEREBRAL CORTEX
The axons of color opponent and double opponent cells , arising from somas in the
LGN , synapse with cells located in several layers of the striate cortex .
The first clue to color organization in the primary visual cortex was the finding of
groups of cells that stain strongly for the presence of cytochrome oxidase .
These groups of cells are referred to as “ blobs “ .
The receptive fields of striate cortical cells located between the blobs are
characteristically tuned to specific spatial orientations , whereas cells within the blobs
have no apparent orientation selectivity .
Blob cells also have relatively simple , concentric , center-surround receptive field
properties , and strongly associated with color differentiation .
It farther appears that the cells of individual blob columns are devoted to one or the
other major types of color opponency : red versus green or blue versus yellow .
Blobs devoted to red/green opponency outnumber those of blue yellow opponency by
a ratio of about 3 to 1 .
In peristriate cortex ( area 18 or V2 ) rather than blobs , the pattern of
cytochrome oxidase staining is one of parallel stripes of alternating widths , thick and
thin .
Cells within the thin stripe regions of area 18 are not orientation selective ,
show a high frequency of color-opponency , and probably receive their input directly
from blob cells of area 17 .
Cells in the thick stripes and in the pale interstripe regions are orientation
selective and are frequently sensitive to binocular disparity ( probably concerned
with stereoacuity .
The thin stripes of area 18 appear to receive most of their input from the blobs of area
17 ,while the pale stripes receive the majority of their input from the interblob regions
of area 17 .
Thus an anatomic and functional segregation of form and color discrimination is
maintained through the striate and into the peristriate visual cortex .
CONGENITAL DYSCHROMATOPSIAS
Two broad groups are represented , those in which reds and greens are confused with
one another and those in which blues and yellows are confused .
Congenital defects in color vision are further subdivided into anomalous trichromacy
, dichromacy , and monochromacy .
Anomalous trichromats are those who still require three primaries in order to match
the full gamut of color but who do not accept matches made by those with normal
color vision .
Dichromats need only two primaries to match any colored light within their spectral
range of vision , and will accept all matches made by normals.
Monochromacy is a term used somewhat confusedly , having been applied to two
different entities .
Rod monochromats are those with a complete congenital absence of cone function ,
while blue cone monochromats have no red or green cone function but appear to have
retinal pigments for both rods and blue cones .
One or more of the normal cone pigments are altered or missing altogether in
individuals affected by congenital dyschromatopsia .
Subjects with complete dichromacy have only two types of cones , each having
normal spectral sensitivity characteristics , with the third type being absent .
Protanopes are dichromats having normal green and blue cones , but an absence of
cones containing long wavelength sensitive pigment .
Conversely , deuteranopes have normal red and blue cones , but an absence of cones
containing the middle wavelength sensitive pigment .
While these subjects appear to have a numerical component of cones, those cones
that should have contained a given variety of pigment ,either red or green , have been
genetically determined to contain the complementary variety .
Anomalous trichromats have three classes of cones , containing three different
pigments , but the pigment in one of the three has an abnormal spectral absorption .
Protanomalous individuals , for instance , lack a normal red-sensitive pigment , but
instead have cones containing pigment with a spectral absorption more nearly like
that of the normal middle wavelength sensitive variety .
As a consequence , the spectral absorption curves of their red and green cones are
more nearly alike .
THE MOLECULAR BIOLOGY OF THE CONGENITAL DYSCHROMATOPSIAS
Congenital dyschromatopsias of the most common variety are caused by alterations in
the genes encoding the red- and green-sensitive photopigments .
Color vision defects are produced by deletions of red or green pigment genes or by
formation of hybrid genes comprised of portions of both red and green pigment genes
, resulting from an unequal crossing over between genes that are located in tandem
within the X chromosome.
Differences in severity of the color vision defects are related to variations in the cross
over sites .
Even among color-normal trichromats , a certain degree of polymorphism has been
found .
Careful studies have shown that normal trichromats can be further subdivided by the
patterns of the color matches that they make with the Rayleigh anomaloscope .
Thus even among color-normals there are detectable ,discrete variations in capacities
for discriminating between middle and long wavelength light .
It is believed that most normal humans have , in fact , more than three different cone
pigment types represented on the X chromosome .
The inherited dyschromatopsias are :
1- binocular
2- symmetrical
3- and do not change over time .
HUE DISCRIMINATION TESTS FOR CHARACTERIZING ABNORMAL
COLOR VISION .
The Fransworth-Munsell 100 hue Test can be used to estimate both the nature and
extent of defective color vision .
The tests consists of a series of 85 colored caps .
The 85 caps are divided into four approximately equal-sized groups that are stored in
separate boxes .
In the course of testing , a subject is asked to arrange the caps in a linear sequence
between pairs of fixed reference caps that are located at either end of each box .
Confusion between similar hues in patients with congenital color defects result in
characteristic patterns in Fransworth-Munsell polar plots .
Transpositional errors are usually confined to restricted zones within the color circle
that are located at directly opposite locations from one another .
ACQUIRED DYSCHROMATOPSIAS
Acquired color vision defects , so called dyschromatopsias , are different from
congenital color vision deficits in several respects .
Most importantly , acquired defects in color vision are noticeable to the observer ,
whereas congenital defects usually are not .
Additionally , acquired defects may be monocular or markedly asymmetric and may
even vary from one part of the visual field to another .
Acquired defects are commonly associated with reduction in visual acuity , changes
in dark adaptations , and/or flicker discrimination .
Acquired deficits are caused by a variety of diseases that damage the retina , the optic
nerve , or the visual cortex .
Toxic , vascular , inflammatory , neoplastic , demyelinating , and degenerative
diseases are all well-recognized causes of acquired dyschromatopsias .
CLASSIFICATIONS OF ACQUIRED DYSCHROMATOPSIAS
Three major types of acquired dyschromatopsias called types I , II , and III are
included in this classification .
The first two varieties are associated with a major axis of hue discrimination in the
red – green region of the Fransworth-munsell diagram , much like the patterns found
for the protan and deutan varieties of congenital dyschromatopsias .
Type I is protanlike , and is manifested as an acquired loss of discrimination between
reds and greens with little or no loss of blue- yellow discrimination .
This variety of dyschromatopsia is also associated with moderate to severe reductions
in VA .
The type II dyschromatopsia is said to be deutanlike , and involves mild to severe
confusion of reds and greens with a simultaneous but milder loss of discrimination
between blues and yellows .
Again type II is usually associated with moderate to severe reductions in VA.
The third type of acquired color vision defect in the Verriest classification , type III ,
is said to be tritan like , and is manifested by mild to moderate confusions of blue and
yellow hues with a lesser or even absent impairment of red –green discrimination . in
this third type of dyschromatopsia VA may be normal or only mildly reduced .
HOW ACQUIRED DISEASES PRODUCE THEIR VARIOUS PATTERNS OF
COLOR DIFICITS .
Because of the small blind spot for blue perception located at the center of the visual
field , human observers making color judgments between the various caps of the
Fransworth-Munsell test must depend on comparisons between the more peripheral
portions of the centrally viewed test objects in oreder to distinguish hues in the blueyellow dimension of color space .
Diseases of the retina and optic nerve produce characteristic patterns of damage in the
central and peripheral portions of the visual field .
For instance , the most common form of glaucoma notoriously damages the
extracentral portions of the visual field , as evidenced by sparing of VA until the
latest stages of the disease .
Apparently selective damage to blue – yellow discrimination with relative
preservation of red-green discrimination and visual acuity ( type III dyschromatopsia
in Verriest classification ) is common in chronic glaucoma .
This should be expected if damage to the extrafoveal visual field ( outside the central
half degree ) exceeds that at the foveal center .
In this situation the higher degree of red-green discrimination and visual acuity found
in the foveal cone mosaic will be relatively preserved , but the perifoveal blue cone
contribution to color discrimination will have been diminished .
THE CENTRAL VISUAL PATHWAY
The ganglion cells are the only cells in the retina that project from the eye to the
brain.
Their axons terminate in a thalamic relay nucleous called the leateral genicualte body
. postsynaptic neurons of lateral geniculate body receiving retinal input project in turn
to the primary visual cortex .
The retino-geniculo-cortical pathway provides the neural substrate for visual
perception .
RETINAL GANGLION CELL TARGETS
Although the lateral geniculate body is the main target of ganglion cells , at least nine
other nuclei within the brain also receive retinal input .
The superior colliculus contains a complete retinotopic map of the contralateral field
of vision .
Application of an electrical pulse to any point on this retinotopic map evokes a
saccade of appropriate direction and amplitude to shift fixation to the receptive field
location of neurons at the stimulation site .
Findings suggest that the superior colliculus is important for visual orienting and
foveation but is not essential for analysis of sensory information leading to visual
perception .
The papillary light reflex is governed by a retinal projection that exits the optic tract
before the lateral geniculate body to terminate bilaterally in a scattered , ill-defined
cellular complex within the midbrain referred to as “ pretectal nuclei “ .
Neurons of pretectal nuclei send projections to the epsilateral and contralateral
Edinger-Westphal subdivisions of the oculomotor nuclei .
Edinger-Westphal neurons provide parasympathetic input via an interneuron in the
ciliary ganglion to control the sphincter pupillae of the iris .
THE RETINO-GENICULO-CORTICAL PATHWAY
RETINA TO LATERAL GENICULATE BODY
The superb visual acuity of humans is achieved at the fovea by thrusting aside all
retinal elements except the photoreceptors , to minimize absorption and scattering of
light .
This unique primate specialization requires fibers from ganglion cells in temporal
retina to follow a circuitous route to the optic disc to avoid passing over the fovea .
The horizontal raphe in the temporal nerve fiber layer results in a complex ,
discontinuous arrangement of ganglion cell axons at the optic disc .
Cells in the temporal retina just above and below the horizontal meridian send their
fibers via a roundabout route to enter the superior and inferior poles of the optic disc
respectively .
Although their cell bodies are situated close together in the retina , their fibers are
widely separated in the optic disc by other fibers that directly enter the nasal and
temporal sides of the disc .
Retinotopic organization is further complicated by intermingling between peripheral
and central axons as they approach the optic disc .
After leaving the eye at the optic disc , the ganglion cell fibers become invested with
myelin to form the optic nerve .
The retinotopic organization of ganglion cell fibers is generally preserved within the
optic nerve .
Near the eye the ganglion cell fibers are precisely arrayed in a manner that duplicates
their arrangement within the optic nerve head .
Moving proximally toward the optic chiasm the fibers gradually scatter in position
until the topography in the optic nerve becomes quite imprecise .
At least a third of the optic nerve is comprised of macular fibers . near the globe the
macular fibers are clustered into the central and temporal sectors of the optic nerve ,
but more proximally they intermingle with other fibers to distribute throughout all
sectors of the optic nerve .
At the optic chiasm the fibers originating from ganglion cells located nasal to the
fovea cross into the contralateral optic tract .
Wilbrand observed that some crossing fibers loop briefly into the opposite nerve
before entering the optic tract ( Wilbrand’s knee ).
At the chiasm the partial decussation of optic nerve fibers merges input from the two
hemiretinas subserving the contralateral field of vision .
THE LATERAL GENICULATE BODY
The lateral geniculate body is the principal thalamic nucleous linking the retina and
the striate cortex . the majority of retinal ganglion cell fibers terminate in the lateral
geniculate body .
The nucleous consists of six principal cellular laminae separated by thin cell-free
zones .
Laminae 1,4,6 receive axons from the contralateral nasal retina and laminae 2,3,5
receive axons from the epsilateral temporal retina .
Each lamina of the LGB contains a precise retinotopic map of the contralateral
hemifield of vision .
Central vision is thought to be represented, in the caudal , 6-layered portion of the
human LGB .
Rostrally , the LGB is reduced to only 4 laminae by fusion of each pair of dorsal
laminae .
The periphery of the visual field is represented in this 4-layered region of the
nucleous .
THE OPTIC RADIATION
Neurons of the LGB complete the relay of retinal input to the primary visual cortex
by projecting to the epsilateral occipital lobe .
Their axons form a sheet of white matter called the optic radiation .
THE PRIMARY VISUAL CORTEX
The upper and lower visual quadrants are represented in the lower and upper
calcarine banks respectively , separated by the horizontal meridian along the base of
the calcarine fissure .
The fovea is represented at the occipital pole .
Most of primary visual cortex is actually buried within the depth of the calcarine
fissure .
The primary visual cortex contains a topographic but highly distorted representation
of the contralateral hemifield of vision .
The most striking feature of the visual field map is the enormous fraction of visual
cortex assigned to the representation of central vision .
Quantitative measurements in macaque monkey reveal that between 55 and 60 % of
the surface area of primary visual cortex is devoted to the representation of the central
10˚ of vision .
The linear cortical ( magnification factor ) – the millimeters of cortex representing
one degree of visual field – has a ratio of more than 40:1 between the fovea ( 0˚
eccentricity ) and the periphery ( 60˚ eccentricity ) .
The representation of central vision is highly magnified compared with peripheral
vision , so that the cortical area devoted to the central 1˚ of visual field roughly equals
the cortical area allotted to the entire monocular temporal crescent .
The relatively magnified representation of the macula in primary visual cortex
furnishes an important clue to how the cerebral cortex analyzes sensory information .
The linear magnification factor of the retina is equal to about 250 micrometers of
tissue per degree for all points in the visual field .
The linear magnification factor of the retina must remain nearly constant , because the
eye is engaged in processing an optical image of the visual environment .
The steep gradient in visual acuity , from 20/20 centrally to 20/400 peripherally , is
achieved by variation in the density of cells in the ganglion cell layer .
In central retina the ganglion cells are stacked 6 to 8 cells deep , declining to a broken
monolayer in peripheral retina .
Free of any optical constrains , the cerebral cortex handles the richer flow of visual
information emanating from the central retina in a different fashion .
The cortical mantle maintains uniform thickness throughout the primary visual cortex
but allocates more tissue for the analysis of central vision .
In the visual cortex the magnification factor , rather than the cell density , varies with
eccentricity in the visual field representation .
From the fovea to the periphery of the visual field a roughly parallel relationship
exists between cortical magnification factor , ganglion cell density .
VISUAL FIELD EXAMINATION
Vision may be impaired by damage to the afferent visual pathway anywhere from the
retina to the occipital lobe .
The preservation of topographic order within the retino-geniculo-cortical pathway
usually allows accurate localization of lesions causing a disturbance in vision by
careful examination of the visual fields .
PRECHIASMAL LESIONS
The crux of visual field analysis is to decide whether a lesion is located before ,at, or
behind the optic chiasm .
A visual field deficit confined to one eye must be due to a lesion anterior to the
chiasm involving either the optic nerve or the retina .
A visual field deficit in both eyes can result from either bilateral prechiasmal lesions
or from a single lesion at or behind the chiasm .
Certain patterns of visual field loss are characteristic of diseases that afflict the optic
nerve .
Glaucoma selectively injures axons that enter the superotemporal and inferotemporal
poles of the optic disc .
This pattern of nerve fiber loss produces arching , fan-shaped field defects that
emanate from the blind spot and curve around fixation to terminate flat against the
nasal horizontal meridian .
This type of field defect, known as Bjerrum scotoma , mirrors the arcuate course of
fibers in the temporal retinal nerve fiber layer .
When the papillomacular bundle is damaged , the patient develops a visual field
defect that encompasses the blind spot and the macula .
This field defect is called a cecocentral scotoma .
The cecocentral scotoma is typical of the optic neuropathy caused by toxins like
ethanol , tobacco , methanol and ethambutol .
Inadequate blood supply to the optic disc results in ischemic optic neuropathy .
This condition is frequently accompanied by an altitudinal pattern of visual field loss .
CHIASMAL LESIONS
The hallmark of chiasmal lesions is bitemporal hemianopia .
For reasons that remain quite unclear , crossed fibers are more vulnerable than
uncrossed fibers to compression of the optic chiasm by mass lesions .
The most common culprit is a tumor arising from the pituitary gland within the sella
turcica .
Lesions situated at the junction of the optic nerve with the optic chiasm can produce
an anterior chiasmal syndrome consisting of blindness in one eye and temporal
hemianopia in the other eye .
POSTCHIASMAL LESIONS
Any lesion behind the chiasm will produce a homonymous hemianopia , namely a
visual field defect involving matching portions of the overlapping temporal hemifield
of the contralateral eye and the nasal hemifield of the epsialteral eye .
It is important to realize that visual acuity will be entirely normal if the postchiasmal
pathway in the other hemisphere is intact .
Input from only half the fovea is sufficient for 20/20 Snellen visual acuity .
A decrement in visual acuity should never be attributed to a unilateral postchiasmal
lesion .
As a general rule : the more congruent a visual field defect,, the more posterior the
lesion in the visual pathway .
Usually a lesion of the optic tract produces a homonymous hemianopia with an
afferent pupil defect in the contralateral eye .
The afferent pupil defect in the contralateral eye occurs because ganglion cells in the
nasal hemiretina outnumber those in the temporal hemiretina .
Consequently , a lesion of the optic tract damages more ganglion cell fibers driving
the pupil reflex of the contralateral eye the epsilateral eye . this results in an afferent
pupil defect in the contralateral eye .
Small lesions of the superior colliculus have been reported to produce an afferent
pupil defect in the contralateral eye with no visual field defect in either eye .
The lesion causes selective injury to the asymmetric pupil fiber input to the
pretectum from the two hemiretinae .
No field defect occurs because retino-geniculate fibers are entirely spared .
An afferent pupil defect will develop after a lesion of the optic tract , but should not
develop after a lesion of the lateral geniculate body , because axons governing the
pupil reflex exit for the midbrain well before the lateral geniculate body .
Lesions involving the optic radiations or the visual cortex do not result in
homonymous hemiretinal atrophy , because the primary projection from the retina to
the lateral geniculate body remains completely intact .
Injury to just a portion of the optic radiations occurs quite frequently and usually
produces a partial homonymous hemianopia that appears roughly quadrantic .
For example , tumors of the temporal lobe may selectively injure Meyer’s loop to
cause a homonymous inferior quadrantanopia .
Partial homonymous hemianopia also occurs from lesions that damage only a portion
of the primary visual cortex .
The conspicuous feature of an incomplete cortical hemianopia is the extreme degree
of congruity . this congruity results because axons from right eye and left eye laminae
of the LGB terminate side by side in a finely dovetailed pattern of the ocular
dominance columns in visual cortex .
MACULAR SPARING
The extreme cortical magnification of the macula is the key to understanding the
problem of macular sparing .
In most individuals the vascular supply to primary visual cortex is provided by the
posterior cerebral artery .after infarction to the territory of the posterior cerebral
artery , a complete , macula-splitting homonymous hemianopia ensues .
However , in some patients the occipital pole straddles the vascular territories of the
posterior cerebral artery and the middle cerebral artery . in these patients the occipital
pole survives after posterior cerebral artery occlusion , due to perfusion by the middle
cerebral artery .
Because the representation of central vision is so magnified , the preservation of
posterior visual cortex spares tissue devoted exclusively to macular vision .
If only the occipital tip becomes infracted , the converse is produced : a homonymous
hemimacular field defect with peripheral sparing .
Complete bilateral injury or infarction of the occipital lobes results in total blindness .
lesions of both optic nerves , tracts , or the chiasm can also cause total blindness .
These two situations can be differentiated by examination of the pupils .
Pupillary responses to light will be absent in patients with total blindness of
infrageniculate origin .
STRUCTURE AND FUNCTION OF THE LATERAL GENICULATE BODY
In the nervous system afferent information from every sensory system except
olfaction passes through the thalamus before reaching the cerebral cortex .
RECEPTIVE FIELD ORGANIZATION
Cells in the visual system discharge action potentials spontaneously even in the
absence of stimulation . For every cell this spontaneous activity can be influenced by
stimulation with light in some region of the visual field .
This special zone is called “ receptive field ” of the cell .
Neurons in the lateral geniculate body share with retinal ganglion cells the same basic
center – surround arrangement of their receptive fields .
On- center cells respond with a burst of spikes when a small spot of light stimulates
the field center .
The maximal response is obtained by choosing a spot size equal to the diameter of the
receptive field center .
If the spot is larger than the field center the cell’s response is attenuated , indicating
antagonism between the center and the surround subfields .
A light annulus suppresses spontaneous activity and produces a brisk “ off ” response.
The inputs of geniculate cells are wired together to generate the more elaborate
receptive fields of cortical cells . Cells in visual cortex are virtually unresponsive to
stimulation with diffuse light .
Information about absolute light intensity is generally not important for the visual
system , except perhaps for the small subclass of retinal ganglion cells that drives the
pupil light reflex .
Information about spatial discontinuities in patterns of light energy is more useful for
image analysis .
Cells with center- surround receptive field organization are ideally suited for
detecting such contrasts .
Their best responses are elicited by contours illuminating just a portion of their
receptive field .
SYNAPTIC INPUTS
Any given optic tract fiber arborizes exclusively within a single geniculate lamina.
Each axon terminal plexus makes about a 100 synaptic contacts over an area 50 to
100 micrometers wide .
Each optic tract fiber may synapse with as few as 4 to 6 geniculate cells and each
geniculate cell receives input from even fewer tract fibers .
A single spike from a retinal ganglion cell fiber is sufficient to elicit a single spike
from a geniculate cell .
On-center ganglion cells trigger only on-center geniculate cells and off-center
ganglion cells drive only off-center geniculate cells .
Some geniculate neurons derive their excitatory input from only a single ganglion
cell. For the majority of geniculate cells the excitatory input is provided by 2 or 3
ganglion cells .
The lateral geniculate body contains about 1800,000 neurons .
Approximately 90% of the retinal ganglion cells terminate in the lateral geniculate
body , yielding a ratio of ganglion cell fibers to geniculate neurons of 1:2 .
This ratio is consistent with data suggesting that each geniculate cell receives input
from 2 to 3 optic tract fibers and that optic tract fiber contacts 4 to 6 geniculate cells .
these average synaptic ratios probably vary with eccentricity and may differ slightly
depending upon the geniculate lamina in question .
MAGNO VERSUS PARVO
A striking difference is apparent in the morphology of neurons in the dorsal laminae
and the ventral laminae of the primate lateral geniculate body.
The two ventral laminae contain loosely packed cells with giant somas that exceed 30
micrometers in diameter .
They are commonly referred to as the magnocellualr laminae .
The four dorsal laminae are comprised of much smaller neurons and hence are known
as the parvocellular laminae .
FUNCTIONAL SPECIFICITY OF GENICULATE LAMINAE
In the primate lateral geniculate body the parvocellular laminae receive input from the
midget retinal ganglion cells , and the magnocellular laminae receive input from the
parasol cells .
This pattern of innervations implies that the color-opponent and broad – band retinal
channels remain segregated at the level of the lateral geniculate body .
In the parvocellular laminae the majority of cells have color-selective responses .
Wiesel and Hubel described three principal types of parvocellular units . the most
common cell ( type 1 ) has a standard center-surround receptive field arrangement .
The center and surround have different spectral sensitivities because they are fed by
different cone systems.
Parvo cells and mango cells differ in other important receptive field parameters
besides their color responses .
At any given eccentricity the receptive fields of mango cells are several times larger
than the fields of parvo cells .
Mango axons conduct action potentials to striate cortex more rapidly than parvo
axons .
Mango cells have higher contrast sensitivity than parvo cells .
To visual stimulation mango cells give rapid , phasic responses whereas parvo cells
give slow , tonic responses .
In parvocellular geniculate the on-center cells and off-center cells are segregated into
separate laminae .
Laminae 5 and 6 receive input mostly from on-center retinal ganglion cells and
consequently contain mostly on-center cells .
Laminae 3 and 4 receive input largely from off-center ganglion cells and are more
richly populated with off-center cells.
This pattern of retinal innervation suggests that one major function of the primate
lateral geniculate body isto sort retinal on-off channels into different laminae .
However , on-center and off-center cells are intermingled through out the
magnocellular geniculate laminae with no loss of specificity in their inputs from oncenter and off-center parasol retinal ganglion cells.
A single excitatory postsynaptic potential from a ganglion cell is usually sufficient to
evoke a discharge from a geniculate neuron .
There is a little divergence or convergence in the transmission of information
throught the lateral geniculate body . In all these respects the LGB appears to behave
as a relay nucleus .
The LGB receives a massive projection from neurons in layer VI of the visual cortex.
This reciprocal corticogeniculate projection might be expected to influence
profoundly the receptive fields of geniculate cells .
It offers an anatomic substrate for potential modulation of retinal inputs at the
geniculate level before transfer to visual cortex .
However , reversible inactivation of the corticogeniculate input by cooling striate
cortex produces only slight effects upon the response properties of cells in the lateral
geniculate body.
This surprising result result leaves us without a clear understanding of the role of the
lateral geniculate body .
THE PRIMARY VISUAL CORTEX
The primary visual cortex is often called “ striate cortex” referring to the prominent
stria found by Gennari .
Later Brodmann parceled the cerebral cortex into 47 different regions based upon
subtle distinctions in cortical histology .
He assigned the arbitrary label of “ area 17 ” to the primary visual cortex .
In recent years other visual areas have been discovered in extrastriate cortex
surrounding the primary visual cortex .
The primary visual has received the prosaic designation of V1 ( visual area 1 )and
adjacent extrastriate visual areas are named V2,V3,V4, and so on.
Primary visual cortex , striate cortex , area 17 and V1 are all synonymous for the
same piece of tissue .
OCULAR DOMINANCE COLUMNS
In a tissue section of visual cortex stained for Nissl substance the most striking
feature is the horizontal lamination of cell bodies .
There are six fundamental layers in the primate cortex .
In striate cortex some layers contain multiple sublayers .
Magno cells and parvo cells project to separate layers of striate cortex in the macaque
monkey .
Magnocellular axons terminate in layer IVCα of striate cortex with minor branches
entering the deeper portion of layer VI .
Parvocellular axons innervate layer IVCβ and layer IVA , with small small additional
inputs to layer I and the upper portion of layer VI .
Layer IVA is absent in humans , indicating that important differences exist among
similar primate species in the cytoarchitecture of striate cortex .
Axon terminals from right eye and left eye geniculate laminae are not randomly
distributed in layer IVC of striate cortex , but rather , they are segregated into a
system of alternating parallel stripes called ocular dominance columns .
In humans the ocular dominance columns have been revealed in striate cortex by
examining the distribution of cytochromoxidase .
Ocular dominance columns are absent in the representation of the temporal
monocular crescent.
Ocular dominance columns are also lacking in the cortical representation of the blind
spot .
At the level of the LGB no binocular interaction occurs , because retinal afferents
terminate in purely monocular laminae .
Convergence of afferents representing the right eye and the left eye occurs only in
striate cortex .
Binocular integration in the cortex is delayed beyond the initial tier of synaptic input
by the segregation of geniculate afferents into ocular dominance columns .
Microelectrode recordings in macaque monkey confirm that neurons in layer IVC are
strictly monocular .
Cells that respond to stimulation from either eye are found only outside layer IV .
such cells owe their binocularity to convergence of inputs from monocular cells in
layer IV .
The functional significance of ocular dominance columns in humans and macaques is
uncertain .
PHYSIOLOGY OF STRIATE CORTEX
Hubel and Wiesel were the first scientists to provide a coherent description of the
receptive field properties of cells in striate cortex .
SIMPLE CELLS
The receptive field of simple cells can be mapped into excitatory and inhibitory
subdivisions with a small spot of light .
They exhibit summation within their separate excitatory and inhibitory subfields and
antagonism when both regions are stimulated simultaneously .
In these respects simple cells are similar to the center-surround cells of the LGB.
The critical distinction between geniculate cells and cortical simple cells lies with the
spatial arrangement of their excitatory and inhibitory domains .
For cortical simple cells these domains are not arrayed concentrically , , but organized
into parallel , flanking subfields separated by straight boundaries .
The geometry of subfields varies considerably among simple cells . In the most
common layout a narrow elongated region , either excitatory or inhibitory , is
sandwiched between two symmetric subregions of the opposite type .
Some cells have subfields of unequal area and other cells have only two antagonistic
subfields .
For all simple cells the best stationary stimulus is a slit or bar of light exactly the right
dimensions to activate only an excitatory ( on-response ) or inhibitory ( off- response
) subfield.
Diffuse light evokes a meager response , because excitatory areas and inhibitory areas
cancel each other .
Correct orientation of the light slit is crucial to obtain the maximum response .
If the stimulating light bar is not parallel to the axis of the receptive field , it will
stimulate part of the inhibitory subfield and fail to stimulate the entire excitatory
subfield .
Orientation selectivity is thus a cardinal feature of cortical simple cells .
For the sake of illustration all the cells in figure are depicted with a preferred
orientation of 45˚ .
In fact , all orientations are represented equally in the visual cortex .
Simple cells also respond briskly to moving bars , slits , or edges and sometimes the
discharge pattern can be predicted from the arrangement of the excitatory and
inhibitory subfields .simple cells usually fire a burst of spikes just as a moving light
slit enters an excitatory region .
The most vigorous discharge is provoked by simultaneously leaving an inhibitory
zone and entering an excitatory zone .
Cells with symmetric subfield arrangements generally give an equal response to
movement in either direction .
Cells with asymmetric subfields often give unequal responses to movement in
opposite directions .
The optimal speed of stimulus movement can also vary among simple cells .
COMPLEX CELLS
The receptive fields of complex cells cannot be mapped with stationary stimuli into
excitatory and inhibitory subregions .
They give inconsistent on-off responses when tested with stationary slits or spots of
light .
However , when a light slit is swept across the receptive field , it elicits a sustained
barrage of impulses .
A complex cell may respond to movement of the light stimulus anywhere within the
receptive field , provided the stimulus is oriented correctly .
By contrast , a simple cell fires only short bursts at the moment when the light slit
crosses an interface between antagonistic subregions .
END-STOPPED CELLS
Ordinary complex cells show summation by responding more robustly as the length
of a light stimulus is increased . the maximum response occurs when a slit or bar
equals the full length of the cell’s receptive field.
Extending the stimulus beyond the length of the receptive field augments the
response no further .
A special subtype of complex cell behaves in a different fashion : the cell’s response
declines sharply as the stimulus exceeds the length of the activating portion of the
receptive field .
RECEPTIVE FIELD HIERARCHY
Receptive fields undergo a remarkable transformation in the progression from the
LGB to striate cortex .
Cells in cortex respond best to suitably oriented bars or edges , rather than circular
spots , and their responses depend critically upon the speed and direction of stimuli .
How do geniculate cells generate the receptive fields of cortical cells ??
Simple cells are concentrated in layer IV of striate cortex , the same cortical layer that
receives the bulk of the projection from the LGB . simple cells are also sprinkled
throughout layer VI , another layer innervated by geniculate neurons .
This finding is unlikely to be a coincidence : it suggests that simple cells receive their
input directly from geniculate cells .
The axons of simple cells ramify widely to synapse upon cells located in other
cortical layers .
Complex cells are common in all cortical layers except layer IV . the logical inference
is that simple cells in layers IV and VI feed their input to complex cells situated
outside layer IV.
Hubel and Wiesel suggested that simple cell receptive fields are constructed from
geniculate cell receptive fields .
For example , the simple field in the figure :
Might be generated by excitatory input from a row of geniculate cells with on-centers
lined up as shown in the figure
In such a scheme a light stimulus falling within the narrow rectangular zone
containing the geniculate on-centers will elicit a net response , despite partial
stimulation of antagonistic field surrounds .
The inhibitory subfields of the simple cell might drive from the off-surrounds of the
geniculate cells , or perhaps from off-center geniculate cells placed in rows on either
side of the on-center units .
The receptive fields of complex cells are probably built from simple cells that share
the same orientation tuning .
In one possible arrangement the receptive fields of simple cells are concatenated
within the larger receptive field of a single complex cell.
A moving light slit will activate in succession each simple receptive field , eventually
exciting a discharge from the complex cell .
A stationary on-off stimulus elicits a feeble response because activation of only one
simple cell is not enough to drive the complex cell .
The role of simple cells and complex cells in visual perception is unclear , although
their receptive field properties are well defined .
Simple cells and complex cells respond best to oriented contours , suggesting that
they process information about borders or edges .
MICROCIRCUIT OF PRIMATE STRIATE CORTEX
A cortical module is comprised of a few million cells. Each cortical module receives
input from only a few thousands geniculate fibers .
The ratio of cortical cells to geniculate afferents ( 106 / 103 ) indicates that after
relatively direct transmission through the lateral geniculate body , the retinal signal
activates a cortical unit containing approximately a thousandfold more processing
elements .
About 15% of the stellate cells in layer IVCβ are inhibitory interneurons .
Both mango and parvo geniculate fibers send collaterals to pyramidal neurons in layer
VI . These pyramidal neurons also receive geniculate input via apical dendrites
branching in layer IVC .
Layer VI pyramidal cells send axon collaterals back to layer IVC , setting up a
reverberating intracortical circuit of unknown function .
The pyramidal cells in layer VI are also believed to give rise to the major reciprocal
projection to the lateral geniculate body .
In summary , striate cortex receives segregated input from two distinct geniculate cell
channels , mango and parvo .
The parvo input goes via layer IVCβ to layers II and III to supply cells within blobs
and between blobs . Blob cells and interblob cells project to separate targets in the
next visual area , V2 .
The mango input proceeds independently from layer IVCα via layer IVB to V2.
EXTRASTRIATE VISUAL CORTEX
According to the classical view , the striate cortex performs a basic analysis of
geniculate input and then transmits some critical essence to higher peristriate cortical
areas for further interpretation .
Visual perception is thought to be enshrined in two visual association areas
surrounding striate cortex , which Brodmann called area 18 and area 19 .
Recent studies in monkeys using physiologic recordings and anatomic tracers have
revealed that areas 18 and 19 together contain at least five distinct cortical areas
devoted to visual processing : V2, V3 , V3A, V4 and V5 .
Other visual areas within and beyond areas 18 and 19 remain to be completely
mapped and characterized .
So far 25 cortical areas predominantly or exclusively engaged in vision have been
identified in the macaque monkey .
The striate cortex constitute the largest single cortical area , averaging 1200 mm2 or
about 12% of the neocortex .
V2 , just slightly smaller than V1 , is the second largest cortical area .
Together , V1 and V2 account for about 20% of the entire surface area of the
neocortex .
After completion of initial processing in striate cortex , visual information is
transmitted to areas V2,V3,V4 and V5 .
Projections unite corresponding retinotopic points in the visual field representation in
each of these cortical areas .
V2 and V3
V1,V2, and V3 are arranged to permit an orderly topographic representation of the
visual hemifield in each area while contact is maximized between adjacent cortical
areas .
V2 and V3 have ventral and dorsal halves that wrap around V1 , as a result the
superior and inferior visual field quadrants are mapped in a retinotopic fashion in V2
and V3 .
The cytochrome oxidase stain reveals an array of coarse parallel stripes in V2 .
The stripes in V2 appear alternately thin and thick , and extend along the full width of
V2 from the V1-V2 border to the V2-V3 border .
Thin stripes receive input from V1 cells located within cytochrome oxidase blobs in
layer II, III .
The thick stripes receive input from V1 cells scattered through out layer IVB .
The pale interstripe zones that separate the thin and thick stripes of intense
cytochrome oxidase activity get their input from V1 cells located between the blobs
in layers II ,III .
V4
This region has come to be known as the color area in extrastriate cortex .
V5 ( middle temporal area )
Neurons in V5 were exquisitely sensitive to stimulus motion .
Some units responded well to alight spot , bar , or slit moved briskly in a preferred
direction and gave no response to an opposite , null direction .
Directional selectivity of cells in such a singular feature of V5 that it has been called
the ( motion area ) in extrastriate cortex .
VISUAL DEPRIVATION
Amblyopia can be defined as a condition caused by abnormal visual experience
during childhood resulting in unilateral or bilateral decrease in acuity that cannot be
explained by a disorder of the eye itself .
Without an ocular explanation for the low acuity , ophthalmologists have speculated
that amblyopia is caused by anomalous wiring of the eye’s central connections in the
brain .
INTRAUTERINE DEVELOPMENT
In the human retina most of the ganglion cells are generated between the eighth and
fifteenth weeks of gestation .
The ganglion cell population reaches a plateau of 2.2 to 2.5 million by week18 and
remains at that level until the thirtieth week of gestation .
After week 30 , the ganglion cell population falls drastically during a period of rapid
cell death that lasts for about 6 to 8 weeks .
Thereafter cell death continues at a low rate through birth and into the first few
postnatal months .
The ganglion cell population is reduced to a final count of about 1 million .
The loss of more than a million supernumerary optic axons may serve to refine the
topography and specificity of the retinogeniculate projection by eliminating
inappropriate connections .
By week 10 the first retinal ganglion cell fibers begin to invade the primordial human
lateral geniculate nucleus .
In the macaque , Rakic has shown that initially the inputs from each eye intermingle
to occupy the entire lateral geniculate body .
The segregation of ocular inputs occurs on a parallel timetable with the development
of lamination .
Retinal afferents prune back their axon terminals so that synaptic connections are
preserved only within appropriate geniculate laminae .
In the human fetus the geniculate laminae emerge between weeks 22 and 25 .
In the macaque monkey the cells destined to comprise striate cortex are born between
days E43 and E102 . This period corresponds to weeks 10 to 25 in the human fetus .
In macaques the geniculate afferents begin to innervate striate cortex by E110 , a time
equivalent to gestational week 26 in humans .
Injection of anatomic tracers reveals that initially the geniculate afferents representing
each eye overlap extensively in layer IVC .
The segregation of inputs into ocular dominance columns transpires during the last
few weeks of pregnancy and is almost complete at birth .
The maturation of the ocular dominance columns requires thousands of left eye and
right eye geniculate afferents to gradually disentangle their overlapping axon
terminals in striate cortex .
NEWBORN FUNCTION
Any parent can testify that the visually guided behavior of human newborns is quite
primitive .
This observation implies that visual acuity is still rather poor at birth .
A number of methods are available to test vision quantitatively in babies .
These techniques rely either upon visual evoked potentials , optokinetic nystagmus ,
or preferential looking by an infant toward a patterned visual stimulus .
Each technique exploits a different approach to measure acuity , but all three
techniques agree fairly well that visual acuity is only 20/400 at birth .
Visual acuity quickly improves to a level of 20/20 within the first few years of life .
This rapid refinement in visual acuity is paralleled by maturation of mechanisms that
control accommodation , stereopsis , smooth pursuit , and saccadic eye movements.
The human macula is immature at birth .
The fovea is still covered by multiple cell layers and only sparsely packed with cones.
During the first year of life the photoreceptors redistribute within the retina and peak
foveal cone density increases by fivefold to achieve the concentration found in adult
retina .
In newborns the white matter of the visual pathway is only scantily clad with myelin .
For the first two years after birth the myelin sheaths enlarge rapidly .
Myelination continues at a slower rate through out the first decade of life .
At birth , neurons of the lateral geniculate body are only 60% of their average adult
size .
Their volume gradually increases until the age of 2 years .
In striate cortex refinement of synaptic connections continues for many years after
birth .
THE ROLE OF ACTIVITY
The visual system begins to form in utero before visual experience can exert any
possible influence .
The continued development of the central visual pathways after birth suggests a
potential for postnatal activity to shape the maturing visual system .
Apparently the basic elements of the cortical module are generated before birth ,
according to instructions that are innately programmed .
Surprisingly , physiologic activity in the fetus plays a vital role in the development of
normal anatomic connections in the visual system .
In utero , mammalian retinal ganglion cells discharge spontaneous action potentials
in the absence of any visual stimulation .
Abolishing these action potentials with tetrodotoxin , a sodium channel blocker ,
prevents the normal prenatal segregation of the retinogeniculate axons into
appropriate geniculate laminae .
Intraocular administration of tetrodotoxin also blocks the formation of ocular
dominance columns in striate cortex .
These experiments indicate that although the functional architecture of the visual
system is ordained by genetics , the specificity and refinement of connections are
molded by physiologic activity occurring in the fetus .
EYELID SUTURE
If a newborn monkey is reared in the dark or with both eyes sutured closed , cells in
striate cortex eventually develop bizarre receptive field properties .
The cells lose sharp orientation tuning and normal binocular responses .
Some cells become oblivious to visual stimulation and can be detected only by virtue
of their erratic spontaneous activity .
The remaining units give sluggish and unpredictable responses to visual stimulation .
After a long period of deprivation , if the monkey is introduced to a normal visual
environment ( or the eyelids are reopened ) , the animal is left profoundly blind with
minimal potential for recovery .
Cells in striate cortex do not recover normal response properties .
These laboratory observations demonstrate that patterned visual stimulation is
required for a critical period after birth to preserve and promote normal visual
function .
In ophthalmology an analogy can be drawn with the newborn baby suffering dense ,
bilateral , congenital lens opacities . In this clinical situation the cataracts must be
removed soon after birth to avoid permanent visual loss from bilateral amblyopia.
Cataract extraction delayed beyond the critical period will not allow the child to enjoy
normal visual function .
If a monkey is visually deprived as an adult by suturing closed both eyelids , there is
no effect upon the properties of cells in striate cortex .
In adult patients , form deprivation induced by slowly advancing cataracts does not
impair visual function in a permanent manner .
After successful removal of the cataracts , the patient experiences full restoration of
sight .
The occluded eye usually develops axial myopia .In the lateral geniculate body the
cells in the deprived laminae become slightly shrunken compared with the cells in
normal laminae .
Although cells within deprived laminae are shrunken , they have normal centersurround receptive fields and respond briskly to visual stimulation . These findings
imply that a defect at the level of the lateral geniculate body is unlikely to account for
amblyopia .
Monocular visual deprivation produces a radical alteration in the ocular dominance
columns in striate cortex .
The ocular dominance columns of the closed eye appear severely narrowed when
labeled with radioactive tracer .
THE CRITICAL PERIOD
The conclusion from performing eyelid closure in different animals at various ages is
that macaque monkeys are vulnerable to the effects of eyelid suture for only a few
months after birth .
This period is defined as the critical period .
In the macaque monkey the closure of one eye any time during the critical period
even for just a week , can result in the shrinkage of ocular dominance columns and
the loss of the deprived eye’s ability to drive cells in striate cortex .
The critical period corresponds to a time when the wiring of the striate cortex is still
malleable and hence vulnerable to the effects of visual deprivation .
During the critical period the deleterious effects of eyelid closure can also be
corrected by reverse eyelid suture .
Reexapansion of deprived eye columns does not occur if reverse suture is carried out
beyond the critical period .
It may explain in part why patching in a child to improve vision in an amblyopic eye
is fruitless if instigated after the end of the critical period .
CLINICAL IMPLICATIONS
The most common etiologies are unilateral ptosis and cataract .
In humans , patching of the normal eye is the mainstay of treatment for amblyopia .
Recent clinical experience suggests that good visual function can be achieved in
children with congenital monocular cataract .
Effective therapy requires early surgical removal of the offending cataract ,
appropriate refractive correction , and vigorous patching of the normal eye .
The critical period in humans has been defined by documenting the visual outcome in
children after surgical removal of congenital cataracts performed at different ages .
These studies indicate that the human critical period extends for at least several years
after birth .
The duration of the critical period may also vary according to the etiology of the
amblyopia .
A minority of cases of amblyopia are caused by media opacity . Other common
etiologies in children include strabismus . , anisometropia , nystagmus , and extreme
refractive error .
Raising an animal with alternate daily occlusion of one eye using a translucent
contact lens leads to selective loss of stereopsis with normal acuity in each eye and
this can be considered a special form of amblyopia due to a breakdown of binocular
connections in striate cortex .
After cutting one extraocular muscle , some monkeys do not alternate fixation but
instead fixate constantly with the same eye . The deviating eye invariably develops
amblyopia .
Few cells in striate cortex can be driven by stimulation of the amblyopic eye .