Metabolic memory: mechanisms and implications for diabetic retinopathy.

Chronic hyperglycemia of diabetes leads to microvascular complications that severely impact quality of life. Diabetic retinopathy (DR) may be the most common of these and is a leading cause of visual impairment and blindness among working age adults in developed nations. Many large-scale type 1 and type 2 diabetes clinical trials have demonstrated that early intensive glycemic control can reduce the incidence and progression of micro and macrovascular complications. On the other hand, epidemiological and prospective data have revealed that the stressors of diabetic vasculature persist beyond the point when glycemic control has been achieved. These kinds of persistent adverse effects of hyperglycemia on the development and progression of complications has been defined as "metabolic memory", and oxidative stress, advanced glycation end products and epigenetic changes have been implicated in the process. Recent studies have indicated that such "hyperglycemic memory" may also influence DR, suggesting that manipulation of hyperglycemic memory may prove a beneficial approach to prevention and treatment. This review summarizes the evidence from DR-related clinical trials and mechanistic studies to investigate the significance of metabolic memory in DR and understand its potential as a target of molecular therapeutics aimed at reversing hyperglycemic memory.