Membrane-bound and soluble Fas ligands have opposite functions in photoreceptor cell death following separation from the retinal pigment epithelium

被引：31

作者：

Matsumoto, H. ^{[1
]}

Murakami, Y. ^{[1
]}

Kataoka, K. ^{[1
]}

Notomi, S. ^{[1
]}

Mantopoulos, D. ^{[1
]}

Trichonas, G. ^{[1
]}

Miller, J. W. ^{[1
]}

Gregory, M. S. ^{[2
]}

Ksander, B. R. ^{[2
]}

Marshak-Rothstein, A. ^{[3
]}

Vavvas, D. G. ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dept Ophthalmol, Angiogenesis Lab,Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA

[2] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Schepens Eye Res I, Boston, MA 02114 USA

[3] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA

来源：

CELL DEATH & DISEASE | 2015年 / 6卷

基金：

日本学术振兴会;

关键词：

APOPTOSIS-INDUCING FACTOR; EXPERIMENTAL-MODEL; CD95; LIGAND; IN-VIVO; DETACHMENT; MACROPHAGES; DEGENERATION; ACTIVATION; RECEPTOR; PATHWAY;

D O I：

10.1038/cddis.2015.334

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Fas ligand (FasL) triggers apoptosis of Fas-positive cells, and previous reports described FasL-induced cell death of Fas-positive photoreceptors following a retinal detachment. However, as FasL exists in membrane-bound (mFasL) and soluble (sFasL) forms, and is expressed on resident microglia and infiltrating monocyte/macrophages, the current study examined the relative contribution of mFasL and sFasL to photoreceptor cell death after induction of experimental retinal detachment in wild-type, knockout (FasL -/-), and mFasL-only knock-in (Delta CS) mice. Retinal detachment in FasL -/- mice resulted in a significant reduction of photoreceptor cell death. In contrast, Delta CS mice displayed significantly more apoptotic photoreceptor cell death. Photoreceptor loss in Delta CS mice was inhibited by a subretinal injection of recombinant sFasL. Thus, Fas/FasL-triggered cell death accounts for a significant amount of photoreceptor cell loss following the retinal detachment. The function of FasL was dependent upon the form of FasL expressed: mFasL triggered photoreceptor cell death, whereas sFasL protected the retina, indicating that enzyme-mediated cleavage of FasL determines, in part, the extent of vision loss following the retinal detachment. Moreover, it also indicates that treatment with sFasL could significantly reduce photoreceptor cell loss in patients with retinal detachment.

引用

页码：e1986 / e1986

页数：9

共 51 条

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