Oxygen supply to the retina
The retina is one of the most metabolically active and high energy demand tissue in the body, which puts it under a persistent demand for a regular supply of oxygen to meet its metabolic needs (1, 2). The major blood supply to the retina is the central retinal artery that is derived from the ophthalmic artery. The ophthalmic artery is branched from the internal carotid artery and goes along the optic nerve (). Oxygen supply to the retina stems from two vascular beds: the choroidal circulation that supplies the outer 1/3 of the retina, and the retinal circulation that supplies the inner 2/3 of the retina (2, 3). The two circulations differ in their vascular ...view middle of the document...
In comparison, during dark adaptation, the photoreceptor region oxygen consumption is substantially increased by about 50% (3), which causes an increase in the oxygen gradient
In summation, there are three high oxygen consumption regions in the retina: The inner segments of the photoreceptor, the outer plexiform layer, and the inner plexiform layer.
The effects of hyperglycemia on intraretinal oxygen profile
Studies have shown no major differences in oxygen profiles in the cat retina during hyperglycemia and normoglycemia (6), where O2 flows down its concentration gradient from the region of the high oxygen tension to the region of the low oxygen tension.
Retinal Oxygen metabolism
The retina has many unique metabolic needs, it has a high oxygen consumption rate to supply ATP that is needed for the high energy demands of the photoreceptor segment, and it depends on glucose to maintain the electrical activity of the retina (7).
The increased levels of glucose due to hyperglycemia alters the electron transport chain in the mitochondria. Hyperglycemia increases the production of the electron donors NADH and FADH2 which increases the proton gradient across the inner mitochondrial membrane inducing membrane potential heterogeneity (2, 8). This sustained gradient leads to the decreased degradation of the electron transport intermediates which increases its concentration leading to the production of superoxide (2). Moreover, the alteration and disruption of the fission and fusion balance in the mitochondria lead to its structural deformation, fragmentation and apoptosis. And the release of cytochrome C, a pro-apoptotic agent (8).
The elevated levels of superoxide production as a result of hyperglycemia can activate and affect four pathways that are suggested to be responsible for retinal microvascular damage and diabetic retinopathy. Super oxide inhibits GAPDH which causes metabolite accumulation. These metabolites are used in the four metabolic pathways that include: The polyol pathway flux, where the major outcome is the decrease of NADPH levels, which is a cofactor needed for the regeneration of reduced glutathione, an important antioxidant (2). Other alteration in the signaling pathway due to increased levels of ROS are the increased advanced glycation end products (AGE), protein kinase C isoforms activation, upregulation of the hexosamine...