Fig. 1

Hyperglycemia-mediated activation of various biochemical pathways. Reactive oxygen species generated due to hyperglycemia increase the transcription of various downstream signalling pathways by damaging the structure of DNA. This halts the normal pathway of glycolysis so that its substrates are diverted to other biochemical pathways. Glyceraldehyde 3 phosphate isomerizes to dihydroxyacetone phosphate (DHAP) that increases the production of advanced glycation end products. Activation of the hexosaminase pathway causes increased o glycosylation of glycolytic substrates. Activation of pyruvate kinase pathway, especially pyruvate kinase beta and NFAT pathway upregulation causes further activation of cytokines, chemokines, and interleukins, having deleterious effects on the cells of the retina, all of which is responsible for the changes of diabetic retinopathy. Activation of the polyol pathway leads to increased production of sorbitol and fructose, which are hyperosmotic agents and are implicated in the causation of diabetic cataract. As glyoxylase enzyme is generally overexpressed in the endothelium, AGE accumulation in the vessel wall is less. However, this detoxification system is deficient in people with diabetes, causing more pericyte apoptosis and thus accentuating DR pathology