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Updated: Aug 26, 2026
Glaucoma-inducing Procedure in an In Vivo Rat Model and Whole-mount Retina Preparation
Published on: March 12, 2016
Retinal ganglion cell protection with geranylgeranylacetone, a heat shock protein inducer, in a rat glaucoma model
Joseph Caprioli1, Yoko Ishii, Jacky M K Kwong
1Department of Ophtalmology, Jules Stein Eye Institute, University of California Los Angeles, School of Medicine, USA.
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.
