gms | German Medical Science

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. Malfunction of the blood retinal barrier plays a central role in the disease and leads to retinal edema and secondary photoreceptor dysfunction. Diabetic vascular leakage and this diabetic macular edema is 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 that with increasing duration of diabetes, the cummulative endothelial cell death will become more relevant.

Leukocyte adhesion in the retinal vasculature is one of the earliest manifestations of diabetic retinopathy. We have previously shown that leukocytes are causally related to capillary non-perfusion, endothelial cell death, and vascular permeability in diabetes. However, the role of inflammation in the pathogenesis of the long-term functional and anatomic pathologies of diabetic retinopathy remains unknown. A chronic, low-grade subclinical inflammation seems responsible for many of the signature vascular lesions of diabetic retinopathy. When compared to age-matched wild type controls, mice deficient in the genes encoding for the leukocyte adhesion molecules (CD18^-/- and ICAM-1^-/-) demonstrate a marked and sustained suppression of retinal vascular leukocyte adhesion, endothelial cell injury, blood-retinal barrier breakdown, pericyte loss and acellular capillary formation. Taken together, these data indicate that diabetic retinopathy is an inflammatory disease, with CD18 and ICAM-1 representing specific therapeutic targets for the prevention of vision loss.