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Nonessential Role of β3 and β5 Integrin Subunits for Efficient Clearance of Cellular Debris after Light-Induced Photoreceptor Degeneration

¹From the Laboratory for Retinal Cell Biology, Department of Ophthalmology, Center for Integrative Human Physiology (CIHP), University of Zürich, Zürich, Switzerland; and ²Novartis Schweiz AG, Bern, Switzerland.

PURPOSE. During light-induced photoreceptor degeneration, large amounts of cellular debris are formed that must be cleared from the subretinal space. The integrins vβ5 and vβ3 are involved in the normal physiological process of phagocytosis in the retina. This study was conducted to investigate the question of whether the lack of β5 and/or β3 integrin subunits might influence the course of retinal degeneration and/or clearance of photoreceptor debris induced by acute exposure to light.

METHODS. Wild-type, β5^–/– and β3^–/– single-knockout, and β3^–/–/β5^–/– Ccl2^–/–/β5^–/– double-knockout mice were exposed to 13,000 lux of white light for 2 hours to induce severe photoreceptor degeneration. Real-time PCR and Western blot analysis were used to analyze gene and protein expression, light- and electron microscopy to judge retinal morphology, and immunofluorescence to study retinal distribution of proteins.

RESULTS. Individual or combined deletion of β3 and β5 integrin subunits did not affect the pattern of photoreceptor cell loss or the clearance of photoreceptor debris in mice compared with that in wild-type mice. Invading macrophages may contribute to efficient phagocytosis. However, ablation of the MCP-1 gene did not prevent macrophage recruitment. Several chemokines in addition to MCP-1 were induced after light-induced damage that may have compensated for the deletion of MCP-1.

CONCLUSIONS. Acute clearance of a large amount of cellular debris from the subretinal space involves invading macrophages and does not depend on β3 and β5 integrins.

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