Most diabetes researchers and clinicians are aware of the major advances made in understanding the pathobiology of proliferative diabetic retinopathy. However mechanisms underlying the progressive alterations in retinal microvessels, which precede and stimulate neovascularization, are less well-known. In this review, current information about the pathogenesis of the primary lesion of diabetic retinopathy, retinal capillary vasoregression (see Fig. 1), is presented.

Diabetic retinopathy is often considered as a complication that contrasts with other vascular sequelae of this disease because it is associated with new vessel formation, while diabetic heart disease and diabetic nephropathy are characterized by impaired angiogenesis (4). Diabetic retinopathy is generally grouped with tumor angiogenesis and is presented as a paradigm of a neovascular disease (5). As outlined in this review, the natural history of diabetic retinopathy starts with vasoregression. Recent investigations have brought new insight regarding the primary vasoregressive process that stimulates angiogenesis, provoking new directions of thinking about possible prevention and intervention (1). Diabetic retinopathy starts with the loss of the two cellular components of retinal capillaries: the pericyte, a vessel support cell, and the endothelial cell. The exact sequence of loss in humans is not established because early human retinal samples are not available, but animal studies have provided evidence that pericytes disappear before endothelial cells start to vanish, leaving acellular capillaries with no blood flow (6). In response to progressive retinal capillary dropout, the ischemic retina mounts an angiogenic response from the surrounding capillaries leading to proliferative diabetic retinopathy. Correlative studies of fluorescein angiography and postmortem retinal