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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)1869-1879
Number of pages11
JournalAmerican Journal of Pathology
Volume162
Issue number6
DOIs
Publication statusPublished - Jun 1 2003

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Phagocytosis
Integrins
glycyl-arginyl-glycyl-aspartyl-seryl-proline
Macrophages
Apoptosis
Retinal Detachment
Photoreceptor Cells
Vertebrate Photoreceptor Cells
Blocking Antibodies
Green Fluorescent Proteins
Bone Marrow Cells
Transgenic Mice
Maintenance
Peptides
Injections
phosphatidylserine receptor

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Clearance of apoptotic photoreceptors : Elimination of apoptotic debris into the subretinal space and macrophage-mediated phagocytosis via phosphatidylserine receptor and integrin αvβ3. / Hisatomi, Toshio; Sakamoto, Taiji; Sonoda, Koh Hei; Tsutsumi, Chikako; Qiao, Hong; Enaida, Hiroshi; Yamanaka, Ichiro; Kubota, Toshiaki; Ishibashi, Tatsuro; Kura, Shinobu; Susin, Santos A.; Kroemer, Guido.

In: American Journal of Pathology, Vol. 162, No. 6, 01.06.2003, p. 1869-1879.

Research output: Contribution to journalArticle

Hisatomi, Toshio ; Sakamoto, Taiji ; Sonoda, Koh Hei ; Tsutsumi, Chikako ; Qiao, Hong ; Enaida, Hiroshi ; Yamanaka, Ichiro ; Kubota, Toshiaki ; Ishibashi, Tatsuro ; Kura, Shinobu ; Susin, Santos A. ; Kroemer, Guido. / Clearance of apoptotic photoreceptors : Elimination of apoptotic debris into the subretinal space and macrophage-mediated phagocytosis via phosphatidylserine receptor and integrin αvβ3. In: American Journal of Pathology. 2003 ; Vol. 162, No. 6. pp. 1869-1879.
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