advertisement
PURPOSE: To investigate whether heat shock protein (Hsp) 72 is induced in retinal ganglion cells (RGCs) in experimental rat glaucoma, and whether the induction of Hsp 72 by heat stress or zinc (Zn24) administration can increase the survival of RGCs in the model. METHODS: Intraocular pressure (IOP) was evaluated unilaterally in Wistar rats with argon laser irradiation of the trabecular meshwork five days after intracameral injection of india ink. Immunohistochemical staining for Hsp 72 was performed. The rats with elevated IOP were treated with heat stress once a week (six rats) or intraperitoneal injection of zinc (10 mg/kg) every two weeks (six rats). Untreated rats with elevated IOP served as a control group (six rats). Quercetin, an inhibitor of Hsp expression, was injected in the rats with heat stress (six rats) and zinc injection (seven rats). Subsequent to four weeks of IOP elevation, RGCs were counted. RESULTS: The IOP increase compared with the contralateral eyes was 48 ± 4% throughout the study period. Hsp 72 was only detected in the eyes with elevated IOP at one and two days and was weakly detected at one week of IOP elevation. A single administration of zinc strongly induced Hsp 72 in RGCs of rats with elevated IOP for two weeks. Treatment with heat stress or zinc in rats with elevated IOP increased RGC survival after four weeks of IOP elevation, compared with the untreated control group (p = 0.004, n = 6). Quercetin reversed the positive effect of heat stress or zinc injection on RGC survival. CONCLUSIONS: These results demonstrate the possibility of a novel therapeutic approach to glaucoma through an enhanced induction of the endogenous heat shock response.
Dr J. Caprioli, Department of Ophthalmology, Jules Stein Eye Institute, UCLA School of Medicine, Room 2-118, 100 Stein Plaza, Los Angeles, CA 90095-7000, USA. caprioli@jsei.ucla.edu
11.8 Neuroprotection (Part of: 11 Medical treatment)
5 Experimental glaucoma; animal models