Opposing roles for membrane bound and soluble Fas ligand in glaucoma-associated retinal ganglion cell death.
Document Type
Article
Publication Date
2011
Keywords
Antigens-CD95, Cell-Death, Cell-Membrane, Cytoprotection, Disease-Models-Animal, Fas-Ligand-Protein, Glaucoma, Injections, Mice-Mutant-Strains, Microglia, Nerve-Fibers, Protein-Binding, Retinal-Degeneration, Retinal-Ganglion-Cells, Signal-Transduction, Solubility, Tumor-Necrosis-Factor-alpha
JAX Source
PLoS One 2011; 6(3):e17659.
Abstract
Glaucoma, the most frequent optic neuropathy, is a leading cause of blindness worldwide. Death of retinal ganglion cells (RGCs) occurs in all forms of glaucoma and accounts for the loss of vision, however the molecular mechanisms that cause RGC loss remain unclear. The pro-apoptotic molecule, Fas ligand, is a transmembrane protein that can be cleaved from the cell surface by metalloproteinases to release a soluble protein with antagonistic activity. Previous studies documented that constitutive ocular expression of FasL maintained immune privilege and prevented neoangeogenesis. We now show that FasL also plays a major role in retinal neurotoxicity. Importantly, in both TNFalpha triggered RGC death and a spontaneous model of glaucoma, gene-targeted mice that express only full-length FasL exhibit accelerated RGC death. By contrast, FasL-deficiency, or administration of soluble FasL, protected RGCs from cell death. These data identify membrane-bound FasL as a critical effector molecule and potential therapeutic target in glaucoma.
Recommended Citation
Gregory MS,
Hackett CG,
Abernathy EF,
Lee KS,
Saff RR,
Hohlbaum AM,
Moody KS,
Hobson MW,
Jones A,
Kolovou P,
Karray S,
Giani A,
John SW,
Chen DF,
Marshak RA,
Ksander BR.
Opposing roles for membrane bound and soluble Fas ligand in glaucoma-associated retinal ganglion cell death. PLoS One 2011; 6(3):e17659.