Abstract
Purpose :
Non-arteritic anterior ischemic optic neuropathy (NAION) is caused by rapid ischemia in the optic nerve head, typically resulting in monocular vision loss. Currently, there are no efficacious drugs available for the pharmacologic management of the disease. The purpose of the present study was to determine the feasibility of targeting the N-methyl-D-aspartate (NMDA) receptor for neuroprotection in a murine model for NAION.
Methods :
NAION was induced in male C57Bl/6J mice using tail vein injection of Rose Bengal followed by lasering the optic nerve with a 532 nm diode laser. Animals were administered either the uncompetitive NMDA receptor antagonist, memantine hydrochloride (MEM, Sigma-Aldrich; n = 5; 50 mg/kg i.p. daily for 7 days) or saline vehicle. Naïve animals (n=4) were used as independent control group. Spectral domain optical coherence tomography (SD-OCT) was used to verify successful model induction. After 7 days, animals were transcardially perfused and retinal wholemounts removed and immunostained against RNA-binding protein with multiple splicing (RBPMS) for quantification of retinal ganglion cells. The total number of RBPMS-positive cells was estimated using stereology.
Results :
SD-OCT confirmed successful induction of retinal damage in all animals; no qualitative differences were observed between MEM- and saline-injected mice. The total number of RBPMS-immunopositive cells was significantly decreased in saline-treated NAION retinas (670 ± 320, mean ± SD) as compared to the contralateral control retinas (1695 ± 210) or retinas from naïve mice (1846 ± 211, Kruskal-Wallis test, P<0.05). There was no significant difference in the number of RBPMS-immunopositive cells of MEM-treated NAION eyes (1650 ± 271) when compared with contralateral control eyes or naïve mouse eyes (P=0.9).
Conclusions :
Systemic administration of MEM can successfully protect RGCs from ischemic damage in the mouse NAION model. Targeting the NMDA-receptor may represent a feasible strategy to develop for the pharmacologic management of NAION.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.