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 FP-TH-09-4 Duration 5min, Q&A 3min Critical Neuroprotecitive Roles of Hemeoxygenase-1 Induction Against Axonal Injury-Induced Retinal Ganglion Cell Death
Objective/Purpose
Axonal damage induced the significant number of retinal ganglion cells (RGCs) death, however small number of RGC was still survival 7 days after optic nerve crush (NC). In order to develop the new treatment of retinal diseases induced by axonal injury, we tried to identify the patterns of gene expression change in these axonal damage resistant RGCs, and put the candidate gene to use for rescuing RGCs. Materials/Patients Adult male wild-type mice (10 to 12 weeks, C57BL/6 male) were used in this study. Methods To overcome the low density of RGCs in the retina, the retrograde-labeling with 4Di-10ASP in the WT mice was performed and purified with fluorescence-activated cell sorting (FACS) of RGC 7 days after NC. Gene expression in the cells was determined with a microarray. The expression of HO-1 mRNA was further confirmed with quantitative PCR (QPCR) and protein was accessed by immunohistochemistry and immunoblotting. In order to investigate the function of HO-1 in RGC death, the density of FluoroGold (FG)-labeled RGCs was counted in retinas from mice pretreated with intraperitoneal injection of CoPP, a potent HO-1 inducer. Results and Conclusion Immunohistochemistry showed that the protein expression of HO-1 was detected in the RGC at 1, 4 and 7 days after NC and the ratio of HO-1 positive cells versus whole RGCs was gradually condensed. The density of FG-labeled RGCs was not significantly changed in vehicle-treated mice (3161 ± 435 cells/mm2), in CoPP-treated mice (3549 ± 475 cells/mm2), and in CoPP- and SnPP-treated mice (3156 ± 658 cells/mm2) without NC. Seven days after NC, the density of surviving RGCs was decreased to 868 ± 252 cells/mm2, while those in CoPP-treated was singnificantly increased (1313 ± 137 cells/mm2, p<0.01). The treatment with SnPP, a HO-1 inhibitor, significantly suppressed the neuroprotective effect of CoPP (808 ± 261 cells/mm2, p<0.05). These results represent changes in HO-1 specific to RGCs that are a key part of RGC survival. Up-regulation of HO-1 signaling may therefore be a novel therapeutic strategy for axonal damage-induced RGC death, such as glaucoma. [ Keyword ] HO-1 / neuroprotection / retinal ganglion cell [ Conflict of Interest ] No |
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