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P Aoun, NJ Patel, JW Simpkins, N Agarwal; PPAR-gamma Ligands Are Neuroprotective Against Glutamate Induced Cytotoxicity in Retinal Ganglion Cells . Invest. Ophthalmol. Vis. Sci. 2002;43(13):748.
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Purpose: The peroxisome proliferator-activated receptor-gamma (PPAR-γ) is the target of the insulin sensitizing thiazolidinediones (TZDs) class of drugs used in the treatment of type II diabetes mellitus. Glaucoma and other retinal pathologies are some of the major complications of diabetes. In our studies we explored the role that PPAR-γ ligands play in protecting retinal ganglion cells against glutamate insult in an in vitro model of glaucoma. Method: Transformed rat RGC (RGC-5 cells) (Mol Brain Res, 2001) and two PPAR-γ agonists: 15-deoxy-delta-12,14-prostaglandin J2(15d-PGJ2) and troglitazone were used. RGC-5 cells were plated in 24-well plates with either of the PPAR-γ ligands and 24 hours later cells were exposed to glutamic acid (5 mM). Cell viability was determined 24 hours after glutamate exposure. Results: A 24-hour glutamate exposure resulted in about 50-60% cell death. Both 15d-PGJ2 and troglitazone protected the RGC-5 cells, in a dose dependent manner, from glutamate toxicity. The neuroprotective concentrations of both compounds ranged from about 500nM to 5µM. Conclusions: Since the RGC-5 cells were shown to behave similarly to non-transformed RGC, they offer a good model to study apoptosis mechanisms related to glaucoma. These results further demonstrate that PPAR-γ ligands may be of therapeutic value in targeting primary retinal pathologies or secondary diabetic complications such as glaucoma.
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