Diabetic Retinopathy: Need for More Research to Understand the Relative Role of Neuropathy and Microvascular Disease

With progression of disease the capillaries of the arterial side of the retinal circulation show increased vasoregression, with cell loss and closure. Simultaneously, the number of microaneurysms increases, and the areas of capillary closure enlarge. As they enlarge, they are seen to be crossed by the remaining enlarged capillaries, which appear to act as arteriovenous shunts, receiving the blood directed from the surrounding closed capillary net. These microvascular lesions, microaneurysms, capillary closure, basement membrane thickening and pericytic damage are different from other vascular retinopathies only in their intensity and distribution [2] . Hyperglycemia appears to be sufficient to initiate the development of DR as revealed by the development of retinopathy in animals experimentally made hyperglycemic [3] . However, the observation that not all patients with poor metabolic control develop advanced stages of DR suggests that other factors, such as genetic predispositions, are likely to determine individual susceptibility to the disease [4] . Even for type 1 diabetes, despite the fact that glycemia is the major risk factor for DR, its overall contribution is only 11%, i.e. 89% of the risk has to be explained by other factors [5] . The retina consists of three major types of cells – neurons, glial cells and blood vessels – and most, if not all, of Diabetic retinopathy (DR) is a frequent complication of diabetes and through its sight-threatening complications, i.e. macular edema and proliferative retinopathy, may lead to blindness. Indeed, DR is the leading cause of vision loss in working age adults (International Diabetes Foundation, 2013). Recent advances in therapy, particularly intravitreal administration of anti-angiogenic agents, have opened new perspectives of vision recovery. However, the availability of treatment only for the late stages of the disease and its rate of success make it urgent to understand the early alterations of DR and their progression in order to develop timely treatments before vision loss. DR is said to be present when microaneurysms and small hemorrhages appear on ophthalmoscopic examination. On histopathological examination, the vascular changes are initiated in the small vessels in the form of endothelial proliferation, pericyte damage and microaneurysms [1] . These initial lesions are focal and located at the posterior pole of the retina. At first the endothelial proliferation and microaneurysms appear to be confined to the venous side of the retinal circulation, whereas at this stage endothelial degeneration appears to be limited to capillaries on the arterial side. The pericyte damage stands out in retinal digests, but their association with microvascular changes is irregular. Received: July 18, 2015 Accepted: July 19, 2015 Published online: August 21, 2015