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Retinal ganglion cell protection with geranylgeranylacetone, a heat shock protein inducer, in a rat glaucoma model.
Invest Ophthalmol Vis Sci. 2003 May; 44(5):1982-92.IO

Abstract

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 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.

RESULTS

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.

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.

Authors+Show Affiliations

Department of Ophthalmology, Jules Stein Eye Institute, University of California Los Angeles School of Medicine, Los Angeles, California 90095-7000, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12714633

Citation

Ishii, Yoko, et al. "Retinal Ganglion Cell Protection With Geranylgeranylacetone, a Heat Shock Protein Inducer, in a Rat Glaucoma Model." Investigative Ophthalmology & Visual Science, vol. 44, no. 5, 2003, pp. 1982-92.
Ishii Y, Kwong JM, Caprioli J. Retinal ganglion cell protection with geranylgeranylacetone, a heat shock protein inducer, in a rat glaucoma model. Invest Ophthalmol Vis Sci. 2003;44(5):1982-92.
Ishii, Y., Kwong, J. M., & Caprioli, J. (2003). Retinal ganglion cell protection with geranylgeranylacetone, a heat shock protein inducer, in a rat glaucoma model. Investigative Ophthalmology & Visual Science, 44(5), 1982-92.
Ishii Y, Kwong JM, Caprioli J. Retinal Ganglion Cell Protection With Geranylgeranylacetone, a Heat Shock Protein Inducer, in a Rat Glaucoma Model. Invest Ophthalmol Vis Sci. 2003;44(5):1982-92. PubMed PMID: 12714633.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Retinal ganglion cell protection with geranylgeranylacetone, a heat shock protein inducer, in a rat glaucoma model. AU - Ishii,Yoko, AU - Kwong,Jacky M K, AU - Caprioli,Joseph, PY - 2003/4/26/pubmed PY - 2003/5/20/medline PY - 2003/4/26/entrez SP - 1982 EP - 92 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 44 IS - 5 N2 - 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 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. RESULTS: 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. 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. SN - 0146-0404 UR - https://www.unboundmedicine.com/medline/citation/12714633/Retinal_ganglion_cell_protection_with_geranylgeranylacetone_a_heat_shock_protein_inducer_in_a_rat_glaucoma_model_ L2 - https://medlineplus.gov/glaucoma.html DB - PRIME DP - Unbound Medicine ER -