UMMS Affiliation

Department of Medicine, Division of Rheumatology

Date

11-19-2015

Document Type

Article

Disciplines

Cell Biology | Cellular and Molecular Physiology | Eye Diseases | Ophthalmology

Abstract

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 (DeltaCS) mice. Retinal detachment in FasL-/- mice resulted in a significant reduction of photoreceptor cell death. In contrast, DeltaCS mice displayed significantly more apoptotic photoreceptor cell death. Photoreceptor loss in DeltaCS 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.

Rights and Permissions

Citation: Cell Death Dis. 2015 Nov 19;6:e1986. doi: 10.1038/cddis.2015.334. Link to article on publisher's site

DOI of Published Version

10.1038/cddis.2015.334

Comments

Cell Death and Disease is an open-access journal published byNature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Related Resources

Link to Article in PubMed

Journal Title

Cell death and disease

PubMed ID

26583327

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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