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Abstract #10165 Published in IGR 6-1
Retinal ganglion cell protection with geranylgeranylacetone, a heat shock protein inducer, in a rat glaucoma model
Caprioli J; Ishii Y; Kwong JMK; Gaasterland DETransactions of the American Ophthalmological Society 2003; 101: 39-51
PURPOSE: To study the effects of geranylgeranylacetone (GGA) on the expression of inducible (HSP72) and constitutive (HSC70) heat shock proteins (HSPs) on retinal ganglion cells (RGCs) in a rat model of glaucoma. METHODS: Adult Wistar rats were given intraperitoneal injections of GGA, 200 mg/kg daily. Western blot analysis and immunohistochemical staining for HSP72 and HSC70 were performed after one, three, and seven days of GGA administration. After seven days of GGA pretreatment, intraocular pressure (IOP) was elevated unilaterally by repeated trabecular argon laser photocoagulation five days after intracameral injection of India ink. After the first laser photocoagulation, GGA was given twice a week. RGC survival was evaluated after five weeks of IOP elevation. Immunohistochemistry and TdT-mediated biotin-dUTP nick end labeling (TUNEL) were performed after one week of IOP elevation. Quercetin, an inhibitor of HSP expression, was also administered to a separate group. RESULTS: There was increased expression of HSP72 in RGCs at three and seven days after GGA administration, but HSC70 was unchanged. After five weeks of IOP elevation, there was 27 ± 6% loss of RGCs. The administration of GGA significantly reduced the loss of RGCs, lessened optic nerve damage, decreased the number of TUNEL-positive cells in the RGC layer, and increased HSP72. Quercetin administration abolished these protective effects. CONCLUSIONS: These results demonstrate that systemic administration of GGA protects RGCs from glaucomatous damage in a rat model and suggest a novel pathway for neuroprotection for patients with glaucoma.
Dr. J. Caprioli, Department of Ophthalmology, Jules Stein Eye Institute, University of California Los Angeles School of Medicine, Los Angeles, CA, USA
Classification:
11.8 Neuroprotection (Part of: 11 Medical treatment)
