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S. Joly, M. Samardzija, M. Thiersch, C. Grimm; Deletions of B3 and/or B5 Integrin Subunits Do Not Influence the Clearance of Cell Debris in the Model of Light-Induced Photoreceptor Degeneration: Evidence for Compensatory Processes. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4418.
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© ARVO (1962-2015); The Authors (2016-present)
Alphav beta3 (b3) and alphav beta5 (b5) integrins are considered as potential mediators of the clearance of photoreceptor debris during phagocytosis. Last year, we demonstrated that the individual deletion of b3 or b5 integrins in single knockouts (KO) led to a differential gene regulation of Caspase-1, MCP-1 (Monocyte Chemoattractant Protein-1, also known as Ccl2) and LIF (Leukemia Inhibitory Factor), but did not induce additional morphological abnormalities after light stress. The purpose of the present study was to better characterize the implication of these integrins in the removal of photoreceptor debris using double knockout mice.
Adult pigmented wild type (WT) mice and double mutant (b3/b5 and Ccl2/b5) mice were exposed to 13,000 lux for 2 hours. At different time points following light offset, retinas and eyecups were separately collected for RNA and protein analysis. mRNA levels were determined by real-time PCR. After light exposure, the extent of histological damages was evaluated on semi-thin sections by light microscopy.
As early as 6 hours after light offset, Caspase-1 mRNA was superinduced by a factor of 2 in b3/b5 KO mice as compared to exposed WT mice while Ccl2/b5 KO mice showed mRNA levels similar to WT. MCP-1 mRNA levels were unchanged in b3/b5 KO mice relative to WT controls at 6 hours after light exposure. In contrast, LIF mRNA was increased 1.7-fold in Ccl2/b5 KO mice at the same time point. Mutant mice presented retinal histology similar to WT mice after light exposure. Surprisingly, in absence of Ccl2 and b5 integrin, light exposed retinae still displayed activated macrophages. Moreover, the levels of Mertk and CD36 receptors mRNA were differentially regulated in eyecups of KO mice compared to WT.
Our data demonstrate that the absence of b3 and/or b5 integrin subunits does not delay phagocytosis and does not cause an accumulation of photoreceptor debris in the subretinal space. Compensatory phenomena are likely to explain the normal clearance of degenerating bodies by RPE and recruited macrophages.
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