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M. Huemmeke, I. Semkova, M. S. P. Ho, C. Frie, M. Plomann, U. Hartmann, A. M. Joussen, M. Paulsson; Basement Membrane Composition in the Normal and Diabetic Retina. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4959.
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The aim of this study is to analyze the molecular composition of basement membranes (BM) in the normal and the diabetic retina. In the retina, they occur in the Bruch`s membrane, the inner limiting membrane (ILM) and as capillary BMs forming part of the blood-retina barrier. All BMs are formed by members of the three protein families, laminins, nidogens, collagen IV, and by the proteoglycan perlecan. While capillary BM thickening is a common observation in diabetic microangiopathy, there is no detailed knowledge of the molecular causes of this phenomenon.
C57B1/6J mice were rendered diabetic (defined by blood glucose > 300 mg/dl) with five consecutive daily intraperitoneal injections of STZ (65mg/kg). After a survival period of 2, 4 or 6 months eyes were enucleated and examined by using histological and immunhistochemical techniques. Fluorescein angiography and flat mount preparations were also performed at different time points. We used a panel of antibodies against the three BM protein families and the proteoglycan perlecan to describe differences in the composition between normal and diabetic retinal BMs.
The normal and diabetic retina showed no marked differences in the immunoreactivity to laminin-1 (highest immunoreactivity in the ILM), collagen IV (moderate intensity in all BMs) and perlecan (mild intensity in all BMs). Laminin-5 showed no immunoreactivity in the retina but high immunoreactivity in the cornea (Bowmann`s membran). Immunoreactivity to nidogen-1 (high in all BM) and nidogen-2 (moderate in all BM) seemed to be increased.Immunoreactivity to the laminin α4 chain (containing in laminin-8, -9 and -14) was enhanced in the capillaries of the diabetic retina (DM4 DM6), while that to the α5 chain (containing in laminin-10, -11 and -15) was less affected.
These data give evidence that there is different participation of laminins, nidogens, collagen IV and perlecan in the BM thickening of the capillaries in diabetic retinopathy. It appears that some laminins and nidogens are upregulated while the levels of collagen IV and perlecan are unchanged. These changes in BM composition may affect both the assembly and function.
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