Introduction: Accelerated formation of AGE due to increasing rise in blood glucose levels leads to developments of metabolic changes, further leading to such complications as diabetic retinopathy which is a major reason of leading to blindness and affecting working population worldwide.Background: The results of recent investigations have demonstrated that the death of retinal ganglion cells (RGCs) and their axons is the common pathological changes in AGE-exposed retina and the possible mechanisms that are responsible for the onset and progression of RGC death and axonal degeneration in patients with diseases associated with AGEs accumulation are represented in this review. Identifying the mechanisms of the onset and the progression of RGC neuropathy can help in discovering the pathogenetic orientated treatment. Objective: This review describes recently discovered possible mechanisms of diabetic retinopathy obtained by laboratory studies with the suggestion that AGEs play an important role in the pathogenesis of diabetic retinal neuropathy triggering different mechanisms that result in neuronal dysfunction. For searching therapeutic approach the regenerative effect of different neurotrophic factors has been studied such as neurotrophin-4, hepatocyte growth factor, glial cell line-derived neurotrophic factor, and Tauroursodeoxycholic acid. Conclusion: The findings for the establishment of neuroprotective and regenerative therapies for AGE-related diseases including diabetic retinopathy are represented in this review.