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Ki Ho Park, Franz Cozier, Olivia C. Ong, Joseph Caprioli; Induction of Heat Shock Protein 72 Protects Retinal Ganglion Cells in a Rat Glaucoma Model. Invest. Ophthalmol. Vis. Sci. 2001;42(7):1522-1530.
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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 (Zn2+)
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
conclusions. These results demonstrate the possibility of a novel therapeutic
approach to glaucoma through an enhanced induction of the endogenous
heat shock response.
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