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Ocular
circulation
D.Waheed Orouk
The blood flow to the eye is of particular interest
because:
:
(1) Many localised and systemic disorders affect the
vasculature of the eye.
(2) The eye has unusual haemodynamic properties because
the tissues are subjected to a high intraocular pressure.
(3) Ocular blood flow is autoregulated - for example,
during changes in retinal illumination, blood pressure, or
posture.
(4) Pharmacological agents which are routinely used in
systemic and ocular diseases may affect the blood supply of
the eye.
The ocular vessels are all derived from
the ophthalmic artery (OA), a branch
of the internal carotid artery. The
retinal and choroidal vessels differ
morphologically and functionally from
each other.
The retinal circulation is an endarterial system without anastomoses.
Astrocytes play important roles in
constraining retinal vessels to the
retina and in maintaining their
integrity.
Blood flow in the normal eye
Total human ocular blood flow is
estimated to be approximately 1
ml/min, most of which supplies
the vasculature of the uvea
(primarily the choroid), only 2-5%
supplying
the retina.
Blood flow in the normal eye
1. Approximately 85% of the total ocular blood flow is in
the choroid.
2. Choroidal blood flow is 20 times greater than that of
retina.
3. Choroidal blood flow is the highest of any system in
the body.
4. The choroidal circulation supplies 80% of the retina
(outer 130 mm – up to the outer part of the inner
nuclear layer), while the retinal vessels supply only
20%.When an eye has a cilioretinal artery, the choroid
supplies the entire thickness of the retina in the area
supplied by the cilioretinal artery.
In the human, the
retinal circulation
has a mean flow
of 0. 033 ml/min.
the
Factors controlling ocular
B.F
1. the vascular 
endothelium
2. perfusion 
pressure
3. nervous 
control
4. effect of drugs
5.metabolic 
Ocular perfusion
pressure is expressed as
the difference between the
arterial BP and the
intraocular pressure (IOP),
which is considered a substitute for the
venous pressure.
ocular perfusion pressure:
A formula has been used to estimate mean
ocular perfusion pressure:
mean OPP=2/3 (DBP+ 1/3 (SBP-DBP))-IOP
where OPP=ocular perfusion pressure,
DBP=diastolic
blood pressure (brachial); SBP=systolic blood
pressure
(brachial); IOP=intraocular pressure.
autoregulation.
The object of blood flow
autoregulation in a tissue is to
maintain relatively constant blood
flow during changes in perfusion
pressure.
This is an important mechanism to
regulate blood flow. The retinal
circulation has efficient
autoregulatory range.
autoregulation.
it most probably operates by
altering the vascular
resistance.
Recent studies have suggested that
pericytes in the retinal capillaries
play a role in autoregulation as well
because of their contractile property.
The metabolic needs of the tissue also
regulate the autoregulation.
Autoregulation works within a critical
range of perfusion pressure, and it breaks
down with any rise or fall of the perfusion
pressure beyond the range critical
autoregulation.
Mechanical stretching and increases in arteriolar
transmural pressure induce the endothelial cells to
release contracting factors affecting the tone of arteriolar
smooth muscle cells and pericytes.
Therefore, damage to vascular endothelium (as in
arteriosclerosis, atherosclerosis,
hypercholesterolemia, aging, diabetes mellitus, ischemia,
and possibly from other causes) may be associated with
abnormalities in the production of endothelial vasoactive
agents, and consequent autoregulation abnormalities.
The regulation of retinal blood flow
is very similar to the regulation of
blood flow in the brain, with the
exception that retinal vessels have
no autonomic innervation and
therefore its regulation depends
even more on the activity of
endothelium cells
.
These cells release a number of
factors, the so-called
endothelium derived
vasoactive factors (EDVFs),
which on one hand regulate the
size of the vessels by influencing
vascular smooth muscle cells
locally, and on the other hand, via
intraluminal release of these
factors lead to changes in blood
rheology (e.g., by influencing
platelet aggregation) .
vascular-endothelial- derived
vasoactive agents
(e.g., endothelin-1,
thromboxane
A2, and prostaglandin H2 –
vasoconstrictors; and
nitric oxide – a vasodilator)
profoundly modulate local vascular
tone and, thereby, may also play a
autoregulation
of blood flow
exists In the
retina,.
The regulation of blood flow of the
choroid is very different from that of
retinal blood flow
.The choroidal vessels are
extensively autonomically
innervated and the capillaries are
fenestrated.
In the uveal tissues autonomic
receptors are present and blood
flow can be altered by
manipulation of the autonomic
system
- for example, stimulation of the
sympathetic system
reduces blood flow whereas cervical
sympathectomy causes
an increase in flow.‘
In contrast with the retinal circulation
autoregulation of flow probably does
not occur in the choroid,.
The difference in the
responses of the retinal and
choroidal circulations is
evident when
ocular perfusion pressure is
reduced, resulting in
reduced choroidal blood
flow while retinal blood
flow remains stable
.
Changes in posture
.
Retinal blood velocities are stable
during postural changes
despite alterations in perfusion
pressure and flow is
effectively autoregulated
metabolites
Autoregulation in the retinal circulation
is controlled by metabolites
,Retinal arteriolar vasoconstriction and venular
dilatation
were observed after high concentration
oxygen breathing.
With variation of blood carbondioxide
levels.‘dilatation of the retinal blood vessels and
shortening of fluorescein dye transit times have,been
detected with increasing arterial partial pressure of
carbon dioxide' in humans
intraocular pressure
Raised intraocular pressure causes a
reduction in blood flow to the anterior
uvea, choroid, and retina.
The retinal blood flow is however
autoregulated up to intraocular
pressures of 30-34 mm Hg after
which the perfusion decreases while
intraocular pressures lower than 10
mm Hg cause the retinal blood flow
to increase
.
dark exposure
In humans increases of 65% in
retinal blood velocity, 5% in
venular diameter, and 82% in
calculated blood flow rate
have been reported in the first
seconds after dark exposure
In contrast, no change in blood
flow in the choroid with dark
adaptation was found
B Blockers and
sympathomimetics
B Blockers and
sympathomimetics may affect
blood flow.
In humans, it was
detected that
vasoconstriction of the
retinal arterioles with
timolol
decreased flow.
acetazolamide
Intravenous
acetazolamide has been
shown to cause
vasodilatation and
increase retinal blood
velocities
,
indomethacin
intravenous administration of
indomethacin induces
a pronounced decrease of
retinal and choroidal blood
flow in humans.
diabetic retinopathy
In diabetic retinopathy retinal
blood flow may be reduced and the
normal autoregulatory capacity be
deficient.
glaucoma
chronic
open angle glaucoma have
studies of patients with
found prolonged dye transit times
on fluorescein videoangiography and
reduced ophthalmic artery
velocities
.
central
retinal vein
occlusion
In central retinal
vein occlusion blood
flow has been shown to
be reduced
oxidative stress.
Metabolism of oxygen by
cells generates as a byproduct
potentially deleterious reactive
oxygen species (ROS)
oxidative stress.
Under optimal conditions the rate and magnitude
of oxidant formation is balanced by the rate of oxidant
elimination through the action of antioxidants.. An
imbalance between prooxidants and antioxidants, in
favour of the former, however, results in oxidative
stress.
This, in turn, may lead to damage of a variety of
macromolecules, such as proteins, lipids, sugar residues,
or
DNA, and thereby leads, in extreme cases, to growth
arrest,
modulation in form and function and even to death of
cells.
Risks and consequences
of oxidative stress. The eye is an
organ that is predisposed to great
levels of oxidative stress. The eye
is constantly exposed to factors such
as radiation, chemicals, oxygen,
drugs, which induce the formation
of reactive oxygen species (ROS)
that can ultimately damage cells.
flickering light
If flickering light hits the eyes, the
vessels dilate within seconds .The exact
mechanism of this regulation is not yet
known. It is known, however, that the
production of nitric oxide (NO) is involved
.
Mechanism of Action of Nitric oxide
Mechanism of Action of Nitric
oxide
NO can directly open potassium channels leading
to cell membrane hyperpolarization.
It is dependent upon the activation of soluble
e
guanylate cyclase (GC) which catalyzes the
conversion of GTP to cyclic GMP.
Cyclic GMP leads to increased levels of Protein
kinase G and the following effects ensue:
e
Stimulation of sodium-potassium adenosine triphosphatase
and opening of adenosine triphosphate-dependent
potassium channels leading to cell membrane
hyperpolarization
Inhibition of phopholipase C and thus decreased production
of stimulatory phosphoinositols.
Stimulates phosphorylation of proteins that accelerate
relaxation.
Inhibition of Rho-kinase which decreases interaction of
contractile proteins.
Cyclooxygenase (COX) is the key enzyme for
the production of several potent
vasoactive substances, including the
prostaglandins (PGs) and
thromboxans.
CO
it has been hypothesized that CO
acts as an endogenously
produced vasoactive factor
analogue to the L-arginine/nitric
oxide system.
Ocular Blood Flow
Measurements