There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Abstract
Adequate function of the retina is dependent on proper oxygen supply. In humans, the
inner retina is oxygenated via the retinal circulation. We present a method to calculate
total retinal oxygen extraction based on measurement of total retinal blood flow using
dual-beam bidirectional Doppler optical coherence tomography and measurement of oxygen
saturation by spectrophotometry. These measurements were done on 8 healthy subjects
while breathing ambient room air and 100% oxygen. Total retinal blood flow was 44.3 ± 9.0 μl/min
during baseline and decreased to 18.7 ± 4.2 μl/min during 100% oxygen breathing (P < 0.001)
resulting in a pronounced decrease in retinal oxygen extraction from 2.33 ± 0.51 μl(O
2)/min to 0.88 ± 0.14 μl(O
2)/min during breathing of 100% oxygen. The method presented in this paper may have
significant potential to study oxygen metabolism in hypoxic retinal diseases such
as diabetic retinopathy.
Optimal retinal neuronal cell function requires an appropriate, tightly regulated environment, provided by cellular barriers, which separate functional compartments, maintain their homeostasis, and control metabolic substrate transport. Correctly regulated hemodynamics and delivery of oxygen and metabolic substrates, as well as intact blood-retinal barriers are necessary requirements for the maintenance of retinal structure and function. Retinal blood flow is autoregulated by the interaction of myogenic and metabolic mechanisms through the release of vasoactive substances by the vascular endothelium and retinal tissue surrounding the arteriolar wall. Autoregulation is achieved by adaptation of the vascular tone of the resistance vessels (arterioles, capillaries) to changes in the perfusion pressure or metabolic needs of the tissue. This adaptation occurs through the interaction of multiple mechanisms affecting the arteriolar smooth muscle cells and capillary pericytes. Mechanical stretch and increases in arteriolar transmural pressure induce the endothelial cells to release contracting factors affecting the tone of arteriolar smooth muscle cells and pericytes. Close interaction between nitric oxide (NO), lactate, arachidonic acid metabolites, released by the neuronal and glial cells during neural activity and energy-generating reactions of the retina strive to optimize blood flow according to the metabolic needs of the tissue. NO, which plays a central role in neurovascular coupling, may exert its effect, by modulating glial cell function involved in such vasomotor responses. During the evolution of ischemic microangiopathies, impairment of structure and function of the retinal neural tissue and endothelium affect the interaction of these metabolic pathways, leading to a disturbed blood flow regulation. The resulting ischemia, tissue hypoxia and alterations in the blood barrier trigger the formation of macular edema and neovascularization. Hypoxia-related VEGF expression correlates with the formation of neovessels. The relief from hypoxia results in arteriolar constriction, decreases the hydrostatic pressure in the capillaries and venules, and relieves endothelial stretching. The reestablished oxygenation of the inner retina downregulates VEGF expression and thus inhibits neovascularization and macular edema. Correct control of the multiple pathways, such as retinal blood flow, tissue oxygenation and metabolic substrate support, aiming at restoring retinal cell metabolic interactions, may be effective in preventing damage occurring during the evolution of ischemic microangiopathies.
We reviewed research on retinal oxygen (O2) distribution and use, focusing on O2 microelectrode studies in animals with circulatory patterns similar to those of humans. The inner and outer halves of the retina are different domains in terms of O2. Understanding their properties can suggest mechanisms of and therapies for retinal diseases. Inner retinal PO2 averages about 20 mm Hg. Effective O2 autoregulation of the retinal circulation ensures that inner retinal PO2 is relatively uninfluenced by systemic hypoxia and hyperoxia and increased intraocular pressure in healthy animals. Failures of the retinal circulation lead to tissue hypoxia that underlies the vasoproliferation in diabetic retinopathy and retinopathy of prematurity. Choroidal blood flow is not regulated metabolically, so systemic hypoxia and elevated intraocular pressure lead to decreases in choroidal PO2 and photoreceptor O2 consumption. The same lack of regulation allows choroidal PO2 to increase dramatically during hyperoxia, offering the potential for O2 to be used therapeutically in retinal vascular occlusive diseases and retinal detachment.
This work is licensed under a Creative Commons Attribution 4.0 International License.
The images or other third party material in this article are included in the article’s
Creative Commons license, unless indicated otherwise in the credit line; if the material
is not included under the Creative Commons license, users will need to obtain permission
from the license holder to reproduce the material. To view a copy of this license,
visit
http://creativecommons.org/licenses/by/4.0/
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.