Department of Medicine, Division of Rheumatology
Cell Biology | Cellular and Molecular Physiology | Eye Diseases | Ophthalmology
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.
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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/.
DOI of Published Version
Cell Death Dis. 2015 Nov 19;6:e1986. doi: 10.1038/cddis.2015.334. Link to article on publisher's site
Cell death and disease
Matsumoto H, Murakami Y, Kataoka K, Notomi S, Mantopoulos D, Trichonas G, Miller JW, Gregory MS, Ksander BR, Marshak-Rothstein A, Vavvas DG. (2015). Membrane-bound and soluble Fas ligands have opposite functions in photoreceptor cell death following separation from the retinal pigment epithelium. Open Access Publications by UMMS Authors. https://doi.org/10.1038/cddis.2015.334. Retrieved from https://escholarship.umassmed.edu/oapubs/2661
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.