Involvement of cell-cell interactions in the pathogenesis of diabetic retinopathy

Retinopathy is a severely disabling complication of diabetes mellitus whose underlying mechanisms are still obscure. The key question is why retinal microvessels are so reactive to the diabetic environment, whereas other microvessels show no evidence of alteration. The answer could lie in the particular structure and location of retinal microvessels since they are composed of, and surrounded by, various types of cells, thereby favouring cell-cell interactions which occur between cells of the capillary wall itself but also with circulating blood cells and retinal neural cells. In the retinal capillary wall, pericytes are in close relation with underlying endothelial cells, and both cell types have close contacts with the capillary basement membrane. Adhesion molecules and cell surface glycoconjugates appear to be the main mediators of interactions between circulating blood cells and capillary endothelial cells, whereas growth factors seem to play a major role in interactions between glial and capillary wall cells in the retina. Biochemical dysfunctions observed in diabetes, such as glycation of proteins and enhanced oxidative stress, could modify these cell-cell and cell-matrix interactions, thereby disturbing the complex cellular organization in which retinal microvessels are embedded. The aim of this review was to provide an overall, nonexhaustive description of some types of cellular interactions that may underlie the pathogenic mechanisms involved in flow and growth changes leading to diabetic retinopathy.