Diabetes and retinal vascular dysfunction

Abstract

Diabetes predominantly affects the microvascular circulation of the retina resulting in a range of structural changes unique to this tissue. These changes ultimately lead to altered permeability, hyperproliferation of endothelial cells and edema, and abnormal vascularization of the retina with resulting loss of vision. Enhanced production of inflammatory mediators and oxidative stress are primary insults with significant contribution to the pathogenesis of diabetic retinopathy (DR). We have determined the identity of the retinal vascular cells affected by hyperglycemia, and have delineated the cell autonomous impact of high glucose on function of these cells. We discuss some of the high glucose specific changes in retinal vascular cells and their contribution to retinal vascular dysfunction. This knowledge provides novel insight into the molecular and cellular defects contributing to the development and progression of diabetic retinopathy, and will aid in the development of innovative, as well as target specific therapeutic approaches for prevention and treatment of DR.

Keywords: Diabetes; Inflammation; Oxidative Stress; Retinal vasculature; Thrombospondins.

Figure 1

Pathophysiology of diabetic retinopathy. Hyperglycemia instigates biochemical changes leading to vascular dysfunction which increases vascular permeability followed by macular edema and retinal neovascularization.

Figure 2

Vascular changes in diabetic retina. Pericytes control vessel stability and proliferation of endothelial cells. Pericyte loss contributes to breakdown of blood-retinal barrier (BRB) and damage to the endothelium, and formation of acellular capillaries. These vascular changes caused by pericyte loss lead to ischemia, proliferative vascularization of retina, and retinal detachment and loss of vision.