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J.M. Hughes, A. Brink, A.N. Witmer, M. Hanraads-de Riemer, I. Klaassen, R.O. Schlingemann, Ocular Angiogenesis Group; Vascular Leukocyte Adhesion Molecules Unaltered in the Human Retina in Diabetes . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3074.
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Capillary occlusion is believed to play a critical role in the development of diabetic retinopathy (DR). The exact mechanism by which it occurs, however, remains unclear. Several in vitro and animal model studies have suggested increased adhesion of leukocytes to the endothelium of the retinal microvasculature as a possible mechanism. Purpose: In this immunohistochemical study we examined this possibility by comparing the presence of several well characterized adhesion molecules in the retinal vasculature of 41 diabetic persons with 19 non-diabetic control subjects. Methods: Monoclonal antibodies (MAbs) against E-selectin, P-selectin, VCAM-1, ICAM-1 and the anti-endothelial MAbs PAL-E and anti-CD31, were used to stain frozen retina sections which were then examined by light microscopy. Results: For all examined adhesion molecules no significant difference was observed in vascular staining between diabetic and non-diabetic persons. E-selectin and VCAM-1 were found to be completely absent in all subjects. P-selectin staining was prominent in the choroidal vasculature while in the retina it occurred sporadically in larger vessels and was often associated with platelets. Vascular ICAM-1 staining was more prominent and occurred in all subjects with the exception of one diabetic subject. We also observed a diffuse ICAM-1 staining of the retina that was significantly more intense in the diabetic subjects (P = 0.001). Conclusions: These results indicate that ICAM-1 and, to a lesser extent, P-selectin, are constitutively expressed on retinal and choroidal vasculature of non-diabetic, control subjects and that this level of expression is not significantly altered by the diabetic environment. Taken together, our results do not support the prevalent paradigm of increased adhesion molecule expression as a primary mechanism responsible for capillary occlusion observed in early stages of diabetic retinopathy.
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