Diabetic Retinopathy: Targeting Vasoregression

  1. Michael Brownlee2
  1. 15th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany;
  2. 2Albert Einstein College of Medicine, New York, New York.
  1. Corresponding author: Hans-Peter Hammes, hans-peter.hammes{at}med5.ma.uni-heidelberg.de.

Diabetic retinopathy is a clinically well-defined, sight-threatening, chronic microvascular complication that eventually affects virtually all patients with diabetes. Diabetic retinopathy is characterized by gradually progressive alterations in the retinal microvasculature, leading to areas of retinal nonperfusion, increased vasopermeability, and in response to retinal nonperfusion, pathologic intraocular proliferation of retinal vessels (13).

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.

FIG. 1.

Phenotype of vasoregression in the diabetic retina. In both experimental diabetic rats and diabetic humans, capillary occlusions occur. Nondiabetic (A) and 6-month diabetic rat retina with acellular capillaries (arrows) (B). Nondiabetic (C) and diabetic (D) human retinal digest preparation. Periodic acid-Schiff staining (original magnification ×250).

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 …

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