Clearance of apoptotic photoreceptors: Elimination of apoptotic debris into the subretinal space and macrophage-mediated phagocytosis via phosphatidylserine receptor and integrin αvβ3

Toshio Hisatomi, Taiji Sakamoto, Koh Hei Sonoda, Chikako Tsutsumi, Hong Qiao, Hiroshi Enaida, Ichiro Yamanaka, Toshiaki Kubota, Tatsuro Ishibashi, Shinobu Kura, Santos A. Susin, Guido Kroemer

研究成果: Contribution to journalArticle査読

79 被引用数 (Scopus)

抄録

The effective phagocytotic 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 well discussed, their phagocytotic process remains quite unclear. We herein demonstrate that apoptotic photoreceptors are selectively eliminated from their physiological localization, the outer nuclear layer, to the subretinal space, and then phagocytosed by monocyte-derived macrophages. This could be shown by an ultrastructural and immunophenotypic analysis. Moreover, in chimera mice expressing transgenic green fluorescent protein in bone marrow-derived cells, the local infiltration of macrophages could be detected after retinal detachment-induced photoreceptor apoptosis. The local injection of an antibody blocking the phosphatidylserine receptor (PSR) or a peptide (GRGDSP)-blocking integrin αvβ3 revealed that phagocytotic clearance involves the PSR as well as integrin αvβ3 in vivo. Importantly, the level of blockade obtained with these reagents was different. Although anti-PSR increased the frequency of apoptotic cells that fail to bind to macrophages, GRGDSP prevented the engulfment (but not the recognition) of apoptotic photoreceptor cells by macrophages. To our knowledge, this is the first report describing the mechanisms through which apoptotic photoreceptors are selectively eliminated via a directional process in the subretinal space.

本文言語英語
ページ(範囲)1869-1879
ページ数11
ジャーナルAmerican Journal of Pathology
162
6
DOI
出版ステータス出版済み - 6 1 2003

All Science Journal Classification (ASJC) codes

  • 病理学および法医学

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