Induction of heat shock protein 72 protects retinal ganglion cells in a rat glaucoma model.
OBJECTIVE
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.
Park
K H
KH
Departments of Ophthalmology and. Neuroscience, Jules Stein Eye Institute, University of California Los Angeles School of Medicine, 90095-7000, USA.
Cozier
F
F
Ong
O C
OC
Caprioli
J
J
D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D002470:Cell Survival / Q000502:physiology; D019610:Cytoprotection; D019084:Fluorescent Antibody Technique, Indirect; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006358:Hot Temperature; D007429:Intraocular Pressure; D008297:Male; D009798:Ocular Hypertension / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D011794:Quercetin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000166:cytology*; D015032:Zinc / Q000494:pharmacology
D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D011794:Quercetin; D015032:Zinc