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Abstract #46301 Published in IGR 13-2
Opposing roles for membrane bound and soluble Fas ligand in glaucoma-associated retinal ganglion cell death
Gregory MS; Hackett CG; Abernathy EF; Lee KS; Saff RR; Hohlbaum AM; Moody KL; Hobson MW; Jones A; Kolovou PPLoS ONE 2011; 6: e17659
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 TNF(alpha) 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
A. Marshak-Rothstein. Department of Medicine, University of Massachusetts Medical School, Worcester, MA, United States. Email: ann.rothstein@umassmed.edu
Classification:
3.6 Cellular biology (Part of: 3 Laboratory methods)
3.9 Pathophysiology (Part of: 3 Laboratory methods)
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
3.7 Biochemistry (Part of: 3 Laboratory methods)
