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Retinal ganglion cell protection with geranylgeranylacetone, a heat shock protein inducer, in a rat glaucoma model.
Trans Am Ophthalmol Soc. 2003; 101:39-50; discussion 50-1.TA

Abstract

PURPOSE

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.

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 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.

RESULTS

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.

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.

Authors+Show Affiliations

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

Pub Type(s)

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

Language

eng

PubMed ID

14971562

Citation

Caprioli, Joseph, et al. "Retinal Ganglion Cell Protection With Geranylgeranylacetone, a Heat Shock Protein Inducer, in a Rat Glaucoma Model." Transactions of the American Ophthalmological Society, vol. 101, 2003, pp. 39-50; discussion 50-1.
Caprioli J, Ishii Y, Kwong JM. Retinal ganglion cell protection with geranylgeranylacetone, a heat shock protein inducer, in a rat glaucoma model. Trans Am Ophthalmol Soc. 2003;101:39-50; discussion 50-1.
Caprioli, J., Ishii, Y., & Kwong, J. M. (2003). Retinal ganglion cell protection with geranylgeranylacetone, a heat shock protein inducer, in a rat glaucoma model. Transactions of the American Ophthalmological Society, 101, 39-50; discussion 50-1.
Caprioli J, Ishii Y, Kwong JM. Retinal Ganglion Cell Protection With Geranylgeranylacetone, a Heat Shock Protein Inducer, in a Rat Glaucoma Model. Trans Am Ophthalmol Soc. 2003;101:39-50; discussion 50-1. PubMed PMID: 14971562.
* 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 - Caprioli,Joseph, AU - Ishii,Yoko, AU - Kwong,Jacky M K, PY - 2004/2/20/pubmed PY - 2004/3/10/medline PY - 2004/2/20/entrez SP - 39-50; discussion 50-1 JF - Transactions of the American Ophthalmological Society JO - Trans Am Ophthalmol Soc VL - 101 N2 - PURPOSE: 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. 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 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. RESULTS: 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. 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. SN - 0065-9533 UR - https://www.unboundmedicine.com/medline/citation/14971562/Retinal_ganglion_cell_protection_with_geranylgeranylacetone_a_heat_shock_protein_inducer_in_a_rat_glaucoma_model_ L2 - https://aosonline.org/assets/xactions/2003/1545-6110_v101_p039.pdf DB - PRIME DP - Unbound Medicine ER -