Ocular circulation D Waheed Orouk The blood flow

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 ascular endothelium ressure n ol n ugs n n

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 A 2, and prostaglandin H 2 – 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 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 studies of patients with chronic open angle glaucoma have 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: en

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