The interphotoreceptor matrix (IPM), referred to clinically as the subretinal space, is the site of interactions between the photoreceptors and pigment epithelium (RPE) which are of fundamental importance to vision. This is the site of a variety of activities which include: retinal attachment; cell-cell recognition before phagocytosis; visual pigment chromophore exchange; establishment of specialized photoreceptor micro-environments; and photoreceptor alignment. The degree of involvement of the components present in the IPM in these activities is not well understood. Defects in the maintenance of the IPM could underlie a variety of clinical disorders which occur at this interface, such as retinal detachment, some forms of macular degeneration, as well as some forms of retinitis pigmentosa. Failure to restore IPM structures could prevent successful reattachment of detached retinas. The long term goal of this research is to elucidate the fundamental processes that establish and maintain the IPM in order to understand better the requirements for photoreceptor survival and optimal function. To achieve this goal, we propose to examine the organization, cellular origin, function, biosynthesis, and development of the multiple constituents of the IPM. With radioactive tracer studies and chromatography in conjunction with cell and organ culture, we will determine the cellular origin of the major IPM components such as chondroitin sulfate proteoglycan (CSPG) in cone matrix sheaths and the wheat germ agglutinin (WGA) binding proteins in rod matrix domains. We will examine the turnover of IPM components in vivo in mice by following changes in specific activity of IPM components after systemic tracer administration. We will determine whether the cone matrix domains function as a barrier to macromolecular movement within the IPM. Finally, we will establish using immunocytochemistry and electron microscopy whether the IPM proteoglycans are present in a higher order of organization as proteoglycan aggregates and establish the various cells which contribute the three components of the aggregate. Forthcoming from these efforts will be a better understanding of the fundamental processes that establish and maintain the IPM and the requirements of these IPM components for photoreceptor survival and optimal function.
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