geranylgeranylacetone and Glaucoma

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.. 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 1, 3, and 7 days of treatment with GGA. After 7 days of GGA pretreatment, intraocular pressure (IOP) was elevated unilaterally by repeated trabecular argon laser photocoagulation 5 days after intracameral injection of india ink. After the first laser photocoagulation, GGA was administered twice a week. RGC survival was evaluated after 5 weeks of elevated IOP. Immunohistochemistry and TdT-mediated biotin-dUTP nick end labeling (TUNEL) were performed after 1 week of elevated IOP. Quercetin, an inhibitor of HSP expression, was also administered to a separate group.. There was increased expression of HSP72 in RGCs at 3 and 7 days after administration of GGA, but HSC70 was unchanged. After 5 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.. 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.

Topics: Animals; Blotting, Western; Cell Count; Cell Survival; Cytoprotection; Disease Models, Animal; Diterpenes; Glaucoma; Heat-Shock Proteins; HSC70 Heat-Shock Proteins; HSP70 Heat-Shock Proteins; HSP72 Heat-Shock Proteins; Immunoenzyme Techniques; In Situ Nick-End Labeling; Injections, Intraperitoneal; Intraocular Pressure; Male; Optic Nerve Diseases; Quercetin; Rats; Rats, Wistar; Retinal Ganglion Cells

To study the effects of geranylgeranylacetone (GCA) on the expression of inducible (HSP72) and constitutive (HSC70) heat shock proteins (HSPs) on retinal ganglion cells (RGCs) in a rat model of glaucoma.. 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 1, 3, and 7 days of GGA administration. After 7 days of GGA pretreatment, intraocular pressure (IOP) was elevated unilaterally by repeated trabecular argon laser photocoagulation 5 days after intracameral injection of india ink. After the first laser photocoagulation, CGA was given twice a week. RGC survival was evaluated after 5 weeks of IOP elevation. Immunohistochemistry and TdT-mediated biotin-dUTP nick end labeling (TUNEL) were performed after 1 week of IOP elevation. Quercetin, an inhibitor of HSP expression, was also administered to a separate group.. There was increased expression of HSP72 in RGCs at 3 and 7 days after GGA administration, but HSC70 was unchanged. After 5 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.. 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.

Topics: Animals; Apoptosis; Cytoprotection; Diterpenes; Glaucoma; Heat-Shock Proteins; HSP72 Heat-Shock Proteins; Rats; Rats, Wistar; Retinal Ganglion Cells