Pathophysiology of Diabetic Retinopathy

Abstract

Diabetic retinopathy is a prototypical microvascular disorder. Hyperglycemia causes a multiple pathological changes in the retinal vasculature. It has been suggested that apoptosis of pericytes due to high glucose levels plays a key role in the development of the earliest events during diabetic retinopathy. Advancement of the disease resulted in a progressive vessel leakage leading to edematous distortion of macula and increase in hypoxia inducing development of neovascularization with sight threatening complications. Four basis hypotheses explaining the hyperglycemia harmful effects were suggested: (1) increased glucose flux through the aldose reductase pathway, (2) overproduction of advanced glycation end products, (3) activation of protein kinase C isoforms, and (4) increased glucose flux via the hexosamine pathway. It was admitted as well that apoptosis of neurons and glial cell activation occur even earlier than vascular damage. Disturbance in glial cell functions leads to increase in metabolic abnormalities such as glutamate accumulation, promotion of inflammation, and oxidative stress resulting in neuron apoptosis and deterioration of vascular disorders. Clarification of significant biochemical mechanisms involving in the development of diabetic retinopathy can help to create new effective ways in diabetic retinopathy treatment.