Diabetic Retinopathy-An Underdiagnosed and Undertreated Inflammatory, Neuro-Vascular Complication of Diabetes

Abstract

Diabetes mellitus is a world-wide epidemic and diabetic retinopathy, a devastating, vision-threatening condition, is one of the most common diabetes-specific complications. Diabetic retinopathy is now recognized to be an inflammatory, neuro-vascular complication with neuronal injury/dysfunction preceding clinical microvascular damage. Importantly, the same pathophysiologic mechanisms that damage the pancreatic β-cell (e.g., inflammation, epigenetic changes, insulin resistance, fuel excess, and abnormal metabolic environment), also lead to cell and tissue damage causing organ dysfunction, elevating the risk of all complications, including diabetic retinopathy. Viewing diabetic retinopathy within the context whereby diabetes and all its complications arise from common pathophysiologic factors allows for the consideration of a wider array of potential ocular as well as systemic treatments for this common and devastating complication. Moreover, it also raises the importance of the need for methods that will provide more timely detection and prediction of the course in order to address early damage to the neurovascular unit prior to the clinical observation of microangiopathy. Currently, treatment success is limited as it is often initiated far too late and after significant neurodegeneration has occurred. This forward-thinking approach of earlier detection and treatment with a wider array of possible therapies broadens the physician's armamentarium and increases the opportunity for prevention and early treatment of diabetic retinopathy with preservation of good vision, as well the prevention of similar destructive processes occurring among other organs.

Keywords: complications; diabetic retinopathy; epigenetics; inflammation; insulin resistance; microvascular; neurodegeneration; neurovascular.

Figure 1

Diabetes and its complications arise from common pathophysiologies. The primary underlying mediator of diabetes complications is the damage due to hyperglycemia and other excess fuels caused by reduced insulin or reduced insulin effect. The development and progression of complications depends on tlhe interplay between genes, epigenetic changes due to the environment, insulin resistance, immune dysregulation and inflammation, fuel excess, and comorbidities (e.g., hyper tension and hyperlipidemia). ASVD, Atherosclerotic vascular disease; DM, Diabetes mellitus; IR, Insulin resistance; NASH, Non-alcoholic steatohepatitis. Source: Schwartz et al. (6). Permission for use of this figure has been obtained.

Figure 2

Pathologic changes to retinal neuro-vascular unit in diabetes. Source: Duh et al. (5). Permission for use of this figure has been obtained.