Induction of heat shock protein 72 protects retinal ganglion cells in a rat glaucoma model.
Autor: | Park KH; Departments of Ophthalmology and. Neuroscience, Jules Stein Eye Institute, University of California Los Angeles School of Medicine, 90095-7000, USA., Cozier F, Ong OC, Caprioli J |
---|---|
Jazyk: | angličtina |
Zdroj: | Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2001 Jun; Vol. 42 (7), pp. 1522-30. |
Abstrakt: | 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 Hsp72 by heat stress or zinc (Zn(2+)) administration can increase survival of RGCs in the model. Methods: Intraocular pressure (IOP) was elevated unilaterally in Wistar rats with argon laser irradiation of the trabecular meshwork 5 days after intracameral injection of india ink. Immunohistochemical staining for Hsp72 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 4 weeks of IOP elevation, RGCs were counted. Results: The IOP increase compared with the contralateral eyes was 48% +/- 4% throughout the study period. Hsp72 was detected only in the eyes with elevated IOP at 1 and 2 days and was weakly detected at 1 week of IOP elevation. A single administration of zinc strongly induced Hsp72 in RGCs of rats with elevated IOP for 2 weeks. Treatment with heat stress or zinc in rats with elevated IOP increased RGC survival after 4 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. |
Databáze: | MEDLINE |
Externí odkaz: |