Download Ciliary Body

Scientific Basis of Vision
Iris, Ciliary Body and Lens
Shiva Swamynathan
Department of Ophthalmology
University of Pittsburgh School of Medicine
Uveal Tract – Vascular middle layer of the eye
Iris (Anterior), Ciliary Body (Middle), Choroid (Posterior)
Iris: Pigmented diaphragm located
between anterior and posterior
chambers. Regulates the amount
of light reaching the retina.
Ciliary Body: Regulates the
composition and production of
aqueous humor, affecting the ionic
environment and metabolism of
the lens, iris, TM and cornea.
Choroid: Vascular layer of the eye
located between the retina and
the sclera. Provides nourishment
and oxygen to outer layers of the
retina.
Where is the uveal tract attached to the sclera?
1. The scleral spur
2. The exit points of vortex veins
3. The optic nerve.
Anatomy of the Iris
Sphincter
Pigmented epithelium
Anterior Border
Stroma
Dilator
Anterior Border- An incomplete layer of endothelial (mesothelial) cells.
The Irideal Stroma accounts for most of the mass of the iris. Composed of connective
tissue, blood vessels and nerve fibers. Pigmented cells containing melanin are
scattered within the stroma. The posterior boundary of the stroma, peripheral to the
sphincter muscle, is demarcated by a sheet of smooth muscle, the dilator muscle.
The pigmented epithelium is composed of two layers of densely pigmented cells.
Blood Supply to the Iris
Source: The major arterial circle in the ciliary body.
The blood vessels of the iris run in a radial direction.
The anterior border layer contains very few vessels.
Innervation of the Iris
The iris is supplied by the ciliary nerves, which pierce the sclera
around the optic nerve and run forward in the perichoroidal space.
After reaching the iris the ciliary nerves form a plexus around its
attached margin, from which the nerve fibers ending in the
anterior surface of the iris, Sphincter and Dilator are derived.
Iridial Muscles- Sphincter and Dilator
(derived from neural ectoderm)
Sphincter muscle. Encircles the pupil, and constricts
the pupil in bright light or during accommodation.
Controlled by parasympathetic nerve fibers.
Dilator muscle. Arranged radially, these fibers
extend from the base of the iris to the sphincter
muscle.
Controlled by sympathetic nerve fibers, although
some parasympathetic fibers are associated with it.
Main functions of iris and ciliary body smooth muscle
1.
2.
3.
4.
Contraction/relaxation
Receptor characterization
Second messenger formation and regulation
Arachidonic acid release and eicosanoid biosynthesis
Ciliary Body
1. Produces aqueous fluid that fills the anterior chamber, maintaining IOP
2. The ciliary muscle facilitates lens accommodation
Pigmented epithelium is leaky while non-pigmented epithelium
facing the aqueous is responsible for the blood-aqueous barrier
What is the rate of aqueous humor production in humans?
About 2-3 ml/min.
How does aqueous humor enter the posterior chamber?
Actively or Passively?
ActivelyPassively-
Energy dependent secretion
carbonic anhydrase-II activity dependent.
Diffusion and Ultrafiltration.
Active secretion accounts for the bulk of aqueous humor
What is the effect of Carbonic Anhydrase-II inhibitors on aqueous flow?
CA-II inhibitors reduce the rate of entry of sodium and bicarbonate into
the aqueous, thus reducing the aqueous humor formation.
Aqueous fluid outflow
The aqueous fluid produced by the
ciliary body flows between the iris and
lens, through the pupil to the drainage
angle at the junction of the iris and
the cornea, and exits the eye through
the trabecular meshwork and
Schlemm’s canal, interscleral channels
and episcleral vein.
True/False: Aqueous humor is rich in macromolecules
False.
Aqueous humor is practically free of macromolecules, allowing for
optical clarity. For example, it contains about 1/500 of the albumin
present in the plasma.
Eicosanoids
Signaling molecules with hormonal activity, made by oxygenation of
20-carbon essential fatty acids. They control inflammation and serve
as messengers in the CNS. They include compounds such as
prostaglandins, prostacyclins, thromboxanes, and leukotrienes.
Eicosanoids are derived from either omega-3 (ω-3) or ω-6 EFAs.
Unlike the ω-3's, ω-6 eicosanoids are generally pro-inflammatory.
Anti-inflammatory drugs such as aspirin and other NSAIDs act by
downregulating eicosanoid synthesis.
They play critical roles in regulating aqueous production and outflow.
Prostaglandin Synthesis
A. In response to cytokines, neurotransmitters or pharmacologic
treatments, phospholipase-A2 is activated, releasing arachidonic
acid from membrane phospholipids
B. Free arachidonic acid is converted to prostaglandin H2
endoperoxide intermediates by cyclooxygenase-I (Cox1;
ubiquitously expressed) or Cox2 (expressed in pro-inflammatory
conditions)
C. Free arachidonic acid can be metabolized through 5’lipoxygenases and cytochrome P-450 pathways to generate
leukotrienes and epoxides, respectively.
D. Phospholipase A2 can be inhibited by corticosteroids;
Cox1 by non-steroidal anti-inflammatory drugs (NSAIDS); and the
5-lipoxygenase pathway by nordihydroguaiaretic acid (NDGA).
True or False?
A. Prostaglandin analogs enhance outflow rather than blocking the
formation of aqueous humor.
B. CA-inhibitors, b-blockers and a2 agonists decrease the formation
of aqueous humor.
C. NSAIDs bind irreversibly to cyclooxygenases blocking biosynthesis
of prostaglandins from arachidonic acid.
D. COX1 is widely and constitutively expressed.
E. COX2 is expressed at low levels in normal physiologic conditions
and upregulated in response to pro-inflammatory signals.
F. COX2 inhibitors (Vioxx, Celebrex, Bextra, etc) increase the risks of
cardiovascular toxicity and complications.
G. Prostaglandin receptors are G-protein coupled 7-transmembrane
domain containing membrane proteins
Neurotransmitters and Receptors in the Iris and Ciliary Body
Muscle
Sphincter
(&Ciliary)
Receptor
Cholinergic
Agonists
Ach, Muscarine
Nicotine
Dilator
Adrenergic
Norepinephrine,
Phenylephrine…
• Sphincter and ciliary muscles contain cholinergic muscarinic type receptors
and are innervated by the parasympathetic third cranial oculomotor nerve.
• Dilator muscles contain a-adrenergic type receptors and are innervated by
sympathetic nerves from the superior cervical ganglion. Adrenergic impulses
are transmitted to the muscles by norepinephrine
• Irideal muscles also contain sensory nerves. Sensory neurotransmitters
substance P and calcitonin gene-related peptide (cgrp) may regulate
inflammatory reactions and irideal muscle tone.
Effect of miotic and mydriatic agents on iris and ciliary muscles
Muscle
Sphincter
(&Ciliary)
Receptor
Cholinergic
Agonists
Ach, Muscarine
Nicotine
Dilator
Adrenergic
Norepinephrine,
Phenylephrine…
Miotic agents
(Constrict the pupil)
Cholinergic agonists stimulate the sphincter
and result in increased accommodation.
Adrenergic blockers block the dilator.
Mydriatic agents
(Dilate the pupil)
Adrenergic agonists stimulate the dilator
Cholinergic blockers block the sphincter and
act as cycloplegics by blocking ciliary muscles.
Mode of action of anti-glaucoma agents
Primary Mechanism of
Action
1. Decreases aqueous
humor production
Drug Class
a. b-adrenergic
antagonists
b. a2-adrenergic
agonists
Examples
a. Timolol, Betaxolol, Carteolol,
Levobunolol
b. Apraclonidine, Brimonidine
2. Increases trabecular a. Miotics
outflow
b. Adrenergic Agonists
a. Pilocarpine
b. Epinephrine, Dipivalyl epinephrine
3. Increases
uveoscleral
outflow
a. Latanoprost, Bimatoprost,
Travoprost
b. Apraclonidine, Brimonidine
a. Prostaglandins
b. a-Adrenergic
Agonists
The choroid
• Posterior segment of the uveal tract, located between retina and sclera
• Provides nutrients and oxygen to the outer layers of the retina
• Blood from the choroidal vessels drains via the four vortex veins
• Choroid is bounded by Bruch's membrane and the sclera
Retinal Pigment Epithelium
Bruch’s Membrane
Choriocapillaris
Medium Choroidal Vessels
Large Choroidal Vessels
Suprachoroidal space
Sclera
Lens
• Lens consists of an external capsule, anterior single cell layered epithelium,
equatorial differentiating zone, and the fiber cells in the rest of the tissue.
• Lens fiber cells are protein-filled sacks lacking nucleus and organelles.
• Lens nucleus consists of the central fiber cells produced from embryonic
through adolescence stage (among the oldest cells in the body).
• Lens cortex consists of the outer fibers laid down after adolescence. New
fiber cells are added to the lens margin throughout life.
Lens Fiber Cell Membranes
• Tightly packed with fairly low fluidity
• High amount of saturated fatty acids
• High cholesterol:phospholipid ratio, and a
• High concentration of sphingomyelin
• Lipids contribute about 1% of total lens mass
Name the major lens-specific integral membrane protein
Aquaporin-0 or Major Intrinsic Protein (Aqp0 or MIP).
Ionic Balance in the Lens
• A sodium-potassium ATPase pump, an intrinsic membrane protein
hydrolyzes ATP, to transport Na+ out and K+ in to the lens.
• Na+-K+-pumps are found primarily in the anterior surface of the
lens, in the epithelium and outer, immature fiber cells.
Intercellular Communication in the Lens
Through gap junctions consisting of connexin 43 in the epithelial
cells and Cx-46 and -50 in the fiber cells.
MIP (Aqp0) also helps in intercellular communication.
Primary Source of Energy in the Lens
Anaerobic glycolysis is the primary source of energy in the lens.
Pentose phosphate pathway is used in oxidative stress conditions,
to replenish NADPH.
Crystallins
Abundant, stable and water-soluble proteins responsible for the
transparent and refractive properties of the lens
Two critical properties of lens crystallins
• Should remain water-soluble at high concentrations
• Should be stable and stay active for a long time
Two classes of crystallins
• Ubiquitous (Present in all vertebrates)
e.g.,a-Crystallin and b/g-crystallins
• Taxon-specific (Different in different species)
e.g., e-crystallin
What is the native molecular mass of a-crystallin?
Larger than 600kDa; can be as high as 1500-2000kDa.
aA- and aB-crystallins are both around 20kDa monomers.
a-crystallin is a super-aggregate of these monomers.
How is spherical aberration avoided by the lens?
Glass bead in water
Decreasing gradient of refractive
index from the centre to the
periphery of the lens resulting from
continual lens development
minimizes the spherical aberration
Fish lens in water
True/False
 b- and g-crystallins are structurally related.
 True
 aB-crystallin is a widely and constitutively expressed member of the small heat
shock proteins family and is inducible by heat and other forms of stress.
 True
 g-crystallin tends to be concentrated in the nuclear region of the lens, as it is
abundantly expressed early in development.
 True
 Most taxon-specific crystallins are oxidoreductases which bind pyridine nucleotides.
Reduced nucleotides absorb UV light, protecting the retina from oxidative damage.
 True
 In the normal lens, concentrations of sodium are low (~10mMol/L) and potassium,
high (~120mMol/L) relative to aqueous humor, which contains high sodium
(~150mMol/L) and low potassium (~5mMol/L).
 True
 The lens displays a smooth gradient of refractive index, which is lowest in the oldest
cells in the center and the highest in the newest cells at the periphery.
 False. Refractive index is the highest at the center and the lowest at the periphery
 aA-crystallin has chaperone-like activity, which is absent in the aB-crystallin.
 False. aB-crystallin also has chaperone like activity.
True/False
1. The lens is avascular and nourished by diffusion from the aqueous
and vitreous.
True
2. The lens capsule is thicker at the anterior, compared to the posterior
of the lens.
True
3. Lens epithelial cells are metabolically active and regulate the water
and ion balance of the entire lens.
True
4. Elimination of cellular organelles is necessary to reduce light scatter.
True
5. Adult lens is surrounded by a single celled epithelial layer.
False
6. Mature lens fibers support active transcription.
False
Questions/Comments?
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