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Abstract #9122 Published in IGR 5-2
Retinal ganglion cell protection with geranylgeranylacetone, a heat shock protein inducer, in a rat glaucoma model
Ishii Y; Kwong JM; Caprioli JInvestigative Ophthalmology and Visual Science 2003; 44: 1982-1992
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 at 200 mg/kg daily. Western blot analysis and immunohistochemical staining for HSP72 and HSC70 were performed after one, three, and seven days of treatment with GGA. 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 administered twice a week. RGC survival was evaluated after five weeks of elevated IOP. Immunohistochemistry and TdT-mediated biotin-dUTP nick end labeling (TUNEL) were performed after one week of elevated IOP. 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 administration of GGA, but HSC70 was unchanged. After five weeks of elevated IOP, there was a 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 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 in patients with glaucoma.
Dr. Y. Ishii, Department of Ophthalmology, Jules Stein Eye Institute, University of California Los Angeles School of Medicine, Los Angeles, CA 90095-7000, USA
Classification:
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
3.6 Cellular biology (Part of: 3 Laboratory methods)
5 Experimental glaucoma; animal models
11.8 Neuroprotection (Part of: 11 Medical treatment)