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 language | English |
|---|---|
| Pages (from-to) | 1869-1879 |
| Number of pages | 11 |
| Journal | American Journal of Pathology |
| Volume | 162 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 1 2003 |
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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 journal › Article
}
TY - JOUR
T1 - Clearance of apoptotic photoreceptors
T2 - Elimination of apoptotic debris into the subretinal space and macrophage-mediated phagocytosis via phosphatidylserine receptor and integrin αvβ3
AU - Hisatomi, Toshio
AU - Sakamoto, Taiji
AU - Sonoda, Koh Hei
AU - Tsutsumi, Chikako
AU - Qiao, Hong
AU - Enaida, Hiroshi
AU - Yamanaka, Ichiro
AU - Kubota, Toshiaki
AU - Ishibashi, Tatsuro
AU - Kura, Shinobu
AU - Susin, Santos A.
AU - Kroemer, Guido
PY - 2003/6/1
Y1 - 2003/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0038243885&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038243885&partnerID=8YFLogxK
U2 - 10.1016/S0002-9440(10)64321-0
DO - 10.1016/S0002-9440(10)64321-0
M3 - Article
C2 - 12759244
AN - SCOPUS:0038243885
VL - 162
SP - 1869
EP - 1879
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 6
ER -