Retinal Vascular Endothelial Cell Dysfunction and Neuroretinal Degeneration in Diabetic Patients

Abstract

Diabetes mellitus (DM) has become a vital societal problem as epidemiological studies demonstrate the increasing incidence of type 1 and type 2 diabetes. Lesions observed in the retina in the course of diabetes, referred to as diabetic retinopathy (DR), are caused by vascular abnormalities and are ischemic in nature. Vascular lesions in diabetes pertain to small vessels (microangiopathy) and involve precapillary arterioles, capillaries and small veins. Pericyte loss, thickening of the basement membrane, and damage and proliferation of endothelial cells are observed. Endothelial cells (monolayer squamous epithelium) form the smooth internal vascular lining indispensable for normal blood flow. Breaking its continuity initiates blood coagulation at that site. The endothelium controls the process of exchange of chemical substances (nutritional, regulatory, waste products) between blood and the retina, and blood cell passing through the vascular wall. Endothelial cells produce biologically active substances involved in blood coagulation, regulating vascular wall tension and stimulating neoangiogenesis. On the other hand, recent studies have demonstrated that diabetic retinopathy may be not only a microvascular disease, but is a result of neuroretinal degeneration. Neuroretinal degeneration appears structurally, as neural apoptosis of amacrine and Muller cells, reactive gliosis, ganglion cell layer/inner plexiform (GCL) thickness, retinal thickness, and retinal nerve fiber layer thickness, and a reduction of the neuroretinal rim in minimum rim width (MRW) and functionally as an abnormal electroretinogram (ERG), dark adaptation, contrast sensitivity, color vision, and microperimetric test. The findings in early stages of diabetic retinopathy may precede microvascular changes of this disease. Furthermore, the article's objective is to characterize the factors and mechanisms conducive to microvascular changes and neuroretinal apoptosis in diabetic retinopathy. Only when all the measures preventing vascular dysfunction are determined will the risk of complications in the course of diabetes be minimized.

Keywords: diabetes; diabetic retinopathy; dysfunction; endothelium; retinal neurodegeneration; retinal vessels.

Figure 1

Possible mechanism of retinal vascular endothelial cell dysfunction and neuroretinal degeneration in diabetic patients. Fundus photos of eyes from diabetic retinopathy accompanied by macular oedema (Panel A), modified from [42]. The neurovascular unit of the retina (retinal ganglion cells, Müller cells, microglia, astrocytes, endothelial cells, pericytes, and other). (Panel B), modified from [43]. The selected factors involved in the development and progression of diabetic retinopathy. AGEs—advanced glycation end products, RAGEs—receptor for advanced glycation end products, VEGF- vascular endothelial growth factor, IGF-I—insulin like growth factor, PLGF—placental growth factor, HGF—hepatocyte growth factor, PEDF pigment epithelium derived factor, bFGF—basic fibroblast growth factor, TGF-beta. transforming growth factor beta, MMPs—metalloproteinases PDGF-platelet-derived growth factor, EGF-Epidermal growth factor, Ang-2—Angiopoietin-2, (Panel C), modified from [42,43].