The effective phagocytic clearance of apoptotic debris is fundamental to the maintenance of neural tissues during apoptosis. Retinal photoreceptors undergo apoptosis after retinal detachment. Although their induction phase of apoptosis has been described, the phagocytic clearing of the apoptotic debris is unclear. In this study, apoptotic photoreceptors are shown to be selectively eliminated from the outer nuclear layer to the subretinal space and then phagocytosed by monocyte-derived macrophages. This was shown by ultrastructural and immunohistofluorescent analysis in experimental retinal detachments in rats. In chimeric mice expressing transgenic green fluorescent protein in bone-marrow derived cells, the local infiltration of macrophages was detected after retinal detachment-induced photoreceptor apoptosis. Local injection of an antibody blocking the phosphatidylserine receptor (PSR) or a peptide (GRGDSP)-blocking integrin αvβ3 revealed that phagocytotic clearance involves the PSR and integrin ανβ3 in vivo. The level of blockade with these reagents was different. Although anti-PSR increased the frequence of apoptotic cells that fail to bind to macrophages, GRGDSP prevented the engulfment (but not the recognition) of apoptotic photoreceptor cells by macrophages.—Hans E. Grossniklaus</P>
American Journal of Ophthalmology – Elsevier
Published: Dec 1, 2003
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