Diabetic Retinopathy

Green W. R.,
Johns Hopkins Hospital, Maumenee Bldg. 427 (Baltimore)

The endothelial cell is the primary target of disease in diabetic retinopathy. Prolonged exposure to high blood glucose levels and other metabolic abnormalities leads to progressive dysfunction of the endothelium manifested as surface changes to the cell which are mediated by defects in signaling mechanisms. Clinically the hallmark of diabetic retinopathy is retinal ischemia due to capillary closure. Capillary closure itself is the result of occlusion by blood cells probably induced by alterations in thrombogenicity of the endothelial surface. Recent investigations have shown that blood leukocytes are activated in diabetes as shown by their increased production of cytokines and shedding of adhesion molecules. Experimentally, closure of capillaries by leukocytes in diabetic animals has been demonstrated while patients with diabetic retinopathy have increased levels of adhesion molecules in their serum and evidence of increased leukocyte adhesiveness to endothelial cells in vitro. Diabetic retinopathy may thus be seen as a dynamic state in which there is continual low-level leukocyte-endothelial adhesion, vascular occlusion, repair and re-adhesion. Eventually, in the presence of uncontrolled disease, vascular occlusion supervenes over tissue perfusion and frank ischemia results. Also hyperglycemia leads to nonenzymatic glycosylation of proteins which become deposited in the vascular wall and contribute to increased vascular permeability, inflammatory cell activation that enhances lipoprotein trapping and modification, and platelets, endothelial cell, and clotting abnormalities. Activation of aldose reductase by elevated blood sugar may also contribute to vascular wall changes and pericyte degeneration. The primary vascular changes induce retinal ischemia which, in turn, leads to neovascularization from the production or release of factors including vascular endothelial, basic and acidic fibroblast, platelet-derived, insulin-like and transforming factor beta, growth factors. The neovascular tissue is accompanied by proliferation of fibrous astrocytes and other cells which contract and the contracted state is maintained by collagen production. The primary retinal histopathologic changes of diabetes include vascular endothelial basement membrane thickening, loss of pericytes, capillary microaneurysms, and, intraretinal vascular abnormalities. Secondary changes include edema, hemorrhages, exudates, microinfarctions of the nerve fiber layer, neovascularization, vitreous hemorrhage, and traction retinal detachment. Future emphasis will be early detection, rigorous glucose control, and the use of factors and substances that inhibit the promoters of the primary and secondary changes.

Copyright © Deutsche Ophthalmologische Gesellschaft, 2002. All rights reserved.

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