Functional Hyperemia and Mechanisms of Neurovascular Coupling in the Retinal Vasculature

Abstract

The retinal vasculature supplies cells of the inner and middle layers of the retina with oxygen and nutrients. Photic stimulation dilates retinal arterioles producing blood flow increases, a response termed functional hyperemia. Despite recent advances, the neurovascular coupling mechanisms mediating the functional hyperemia response in the retina remain unclear. In this review, the retinal functional hyperemia response is described, and the cellular mechanisms that may mediate the response are assessed. These neurovascular coupling mechanisms include neuronal stimulation of glial cells, leading to the release of vasoactive arachidonic acid metabolites onto blood vessels, release of potassium from glial cells onto vessels, and production and release of nitric oxide (NO), lactate, and adenosine from neurons and glia. The modulation of neurovascular coupling by oxygen and NO are described, and changes in functional hyperemia that occur with aging and in diabetic retinopathy, glaucoma, and other pathologies, are reviewed. Finally, outstanding questions concerning retinal blood flow in health and disease are discussed. In lower vertebrates that have thinner retinas, including amphibians, reptiles, and some mammals, the retinal vasculature is absent and the choroidal circulation supplies the entire retina. 2 The choroidal circulation is supplied by the long and short ciliary arteries and the anterior ciliary arteries, which feed the large arteries in the outer portion of the choroid. 3 These arteries branch into smaller vessels, which, in turn, feed the highly anastomosed choriocapillaris network lying at the inner border of the choroid, adjacent to the retinal pigment epithelium and retinal photoreceptors. The total blood flow supplying the choroid is much greater than that supplying the retina (606 vs. 25 mg/min/ whole tissue 4 ), to meet the high metabolic demands of the photoreceptors. 5 The retinal vasculature is supplied by the central retinal artery, which enters the retina with the optic nerve at the optic disc. The artery branches into radial arterioles and smaller vessels on the vitreal surface of the retina. 3 Pre-capillary arterioles and capillaries ramify from these surface vessels and form anastomotic networks in the ganglion cell layer, just beneath the retinal surface, and deeper in the inner nuclear layer, supplying horizontal cells, bipolar cells, amacrine cells, and Mü ller glial cells. Blood is returned through radial venules on the retinal surface that empty into the central retinal vein in the optic nerve. Journal of Cerebral BloodThe retinal and choroidal vasculatures differ in several respects. Retinal vessels lack autonomic innervation, 6,7 whereas the choroidal circulation is innervated by both sympathetic and parasympathetic

Endothelial dysfunction in cardiovascular disease and Flammer syndrome—similarities and differences

“…The exact pathways involved in neuro-glia-vascular coupling are not fully understood. Likely, oxygen demand in response to flicker light increases [62] and stimulated neurons signal a calcium concentration surge in Müller glia that release vasodilatory prostaglandin E2, NO, and epoxyeicosatrienoic acids [63,64]. The gliovascular unit, thus, relaxes the smallest arteriolar walls.…”

Glial cell regulation of neuronal activity and blood flow in the retina by release of gliotransmitters

“…Suramin, a non-selective purinergic antagonist completely blocks , which converts membrane phospholipids (MPL) to arachidonic acid (AA) which is subsequently metabolized to the vasodilators prostaglandin E 2 (PGE 2 ) and epoxyeicosatrienoic acids (EETs), and to the vasoconstrictor 20-hydroxy-eicosatetraenoic acid (20-HETE). (a -f ) From Metea & Newman [18] and (g) adapted from Newman [20]. (Online version in colour.…”

Human retinal imaging using visible-light optical coherence tomography guided by scanning laser ophthalmoscopy

“…One question is whether the visible laser beam will affect retinal physiology, particularly when using vis-OCT to perform quantitative measurements such as blood flow and sO 2 . It has been found that both flow and retinal metabolism change when the retina transitions from dark adaptation to light or under flicker stimulation [31][32][33]; however, we do not expect such changes to occur when the retina has already been light-adapted [34,35]. The additional exposure from vis-OCT is unlikely to change the physiological condition of the eye, thereby underscoring the importance of ensuring the patient's eye is light-adapted before vis-OCT imaging.…”