Pathogenesis of Diabetic Maculopathy
Joussen A. M.
Department of Vitreoretinal Surgery, Center for Ophthalmology, University of Cologne
Diabetic maculopathy is the leading cause of visual loss in diabetic patients. The pathogenesis is not fully understood and a satisfactory therapy is currently not available.
Increased leukocyte adhesion to the retinal vasculature in diabetes is associated with these findings and the observed endothelial cell injury and vascular leakage can be prevented by inhibition of leukocyte adhesion. Retinal cells are capable of Fas-mediated apoptosis and FasL is upregulated on the cell surface of leukocytes by diabetes. Furthermore, leukocytes from diabetic animals are capable of inducing Fas-mediated endothelial cell injury, resulting in capillary damage and retinal vascular permeability. These data suggest a mechanistic role for Fas/FasL in the development of diabetic retinopathy and macular edema and imply that inhibition of the Fas/FasL system may prove beneficial in treating retinal complications of diabetes. Besides direct endothelial cell death growth factors such as VEGF and the angiopoietin family and alterations in various junction molecules are involved in the increased vascular leakage in diabetes.
In conclusion diabetic vascular leakage and diabetic macular edema are regulated by a distinct combination of direct paracellular transport, alterations in the cell-cell junctions of endothelial cells and cell death of these endothelial cells. With increasing duration of diabetes, the relative relevance of these three components varies, and the cummulati
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