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Reiko Yamagishi, Megumi Honjo, Makoto Aihara, Chui Yong Ku; Effect of ripasudil on NMDA-induced retinal damage in mouse eye.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):623.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the effect of Ripasudil, a Rho-kinase inhibitor which lowers intraocular pressure by enhancement of trabecular aqueous outflow, in NMDA-induced retinal damage in mice.
10mM NMDA and various concentrations of ripasudil (rip) were simultaneously injected to vitreous in CFP mice. The estimated intravitreal concentration of ripasudil were 1,10 and 100μM. One week after, the eyeball was removed, and the number of retinal ganglion cells (RGCs) were counted at retinal flat mount. The retinal thickness was also measured in living mice by optical coherence tomography (OCT) after 1, 2 and 3 weeks of injection. Furthermore, in order to investigate the changes of oxidative stress related to retinal damage, the reduced glutathione concentration (GSH) in the retina after 1, 3 and 5 days of administration was measured using the GSSG / GSH Quantification Kit.
RGCs of vehicle, NMDA, NMDA+1μM rip, NMDA+10μM rip and NMDA+100μM rip-treated groups were 292±92, 457±153, 509±342, 678±500 and 1215±277 cells/mm2 at 1week after injection, respectively. RGCs were significantly decreased in NMDA-treated group compared to vehicle-treated group (p<0.05), and the RGCs loss in NMDA+100μM rip-treated group was significantly suppressed compared to NMDA-treated group at one week after injection (p <0.05). The retinal thickness was significantly decreased in the NMDA-treated group at 2 weeks after injection (p <0.05), and the retinal thickness reduction was significantly inhibited in NMDA + 100μM rip-treated group at 3 weeks after injection (p <0.05). Furthermore, GSH in the retina significantly increased in the NMDA group 3 days after injection, and the NMDA + 100μM Rip-treated group showed significantly suppressed GSH increase induced by NMDA injection (p <0.05).
Ripasudil suppressed retinal damage induced by NMDA in mice via anti-oxidative effect, which could be useful as an additive effect of this anti-glaucoma medicine in an intraocular pressure-independent manner.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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