Basement membrane composition in the normal and diabetic retina

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Basement membranes are required for cellular adhesion, migration and differentiation. They also play a particular role in the delimiting of tissue boundaries and the formation of vascular and neural networks. Changes in the deposition of the extracellular matrix during diabetes mellitus are well established; however the molecular composition of the basement membranes in the normal and diabetic retina is only poorly described. Further, alterations in the repertoire of cellular receptors for basement membrane components and the effects these changes have upon the cells of the retina have not been thoroughly investigated. We will use a panel of antibodies against the main basement membrane proteins and their receptors to describe the composition of the retinal basement membranes in the normal mouse and in two mouse models of diabetes mellitus. Mice at various stages of the disease will be studied. Once candidate proteins with a changed expression profile have been identified they will be examined for their expression pattern in the diseased human eye. Finally, where available, mice carrying null mutations for these proteins will studied for the presence of any ocular phenotype and will be bred to the diabetic model strains and any modulation in the course of the pathology will be described. This will allow determining the significance in the basement membrane changes in the development of diabetic retinopathy.