Heat shock protein 72 protects retinal ganglion cells in rat model of acute glaucoma.

Purpose: To investigate whether the induction of heat shock protein (HSP)72 by heat stress (HS) or zinc (Zn2+ ) administration can increase survival of retinal ganglion cells (RGC)in rat model of acute experimental glaucoma.

Methods: Acute glaucoma model was made by intracameral irrigation with BSS at 10(2) mmHg for two hours in right eyes of male Wistar rats. Glaucoma model rats were treated with HS once a week (six rats) or intraperitoneal injection of zinc sulfate (24.6 mg/kg) every two weeks (six rats), and were referred to as HS group and zinc group, respectively. Untreated model rats served as damage group (six rats). In control groups, quercetin (400 mg/kg) was intraperitoneally injected to inhibit the induction of heat shock proteins 6 hours before HS or zinc administration, and were referred to as HS+que group (six rats) and zinc+que group (six rats), respectively. Subsequent to 16 days of IOP elevation, the rats were sacrificed. Eyes were quickly enucleated, and the retinas were dissected. RGC were labeled with Nissl staining and counted under microscope.

Results: The average RGC density in normal Wistar rats was (2504+/-181) cells/mm(2). In damage group, it decreased to (2015+/-1111) cells/mm(2). The RGC densities at 1, 2, and 3 mm from the center of the optic nerve head were (2716+/-215), (2496+/-168), and (2317+/-171) cells/mm(2), respectively, for normal rats and (2211+/-133), (1969+/-154), and (1872+/-68) cells/mm(2), respectively, for damage group. The latter was significantly lower at all locations compared with the former (P=0.027 for each, Mann-Whitney test). The average RGC densities were (2207+/-200) cells/mm(2) for HS group, (2272+/-155) cells/mm(2) for zinc group, (1964+/-188) cells/mm(2) for HS+que group, (2051+/-214) cells/mm(2 )for zinc+que group and (2015+/-111) cells/mm(2) for damage group. There were significant differences in density of labeled RGCs among the five groups (P=0.040, Kruskal-Wallis test). Both HS and zinc group had higher RGC densities than damage group (P =0.036 between HS and damage group, P=0.019 between zinc and damage group, Mann-Whitney test). There was no significant difference in RGC density between control groups and damage group(P=-0.260 between HS+que and damage group, P-0.748 between zinc+que and damage group, Mann-Whitney test).

Conclusions: The results demonstrated that the induction of HSP72 in RGCs by HS or zinc administration plays an important role in the survival of RGCs in rat model of acute glaucoma. A novel therapeutic approach to glaucoma through an enhanced induction of endogenous HSP72 could be possible.