July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Neuroprotection of retinal ganglion cells via NMDA-dependent mechanism in the mouse non-arteritic anterior ischemic optic neuropathy (NAION) model
Author Affiliations & Notes
  • Symantas Ragauskas
    Experimentica ltd, Kuopio, Finland
  • Agne Ziniauskaite
    Experimentica ltd, Kuopio, Finland
  • Simon Kaja
    Experimentica ltd, Kuopio, Finland
    Department of Ophthalmology, Loyola University Chicago, Maywood, Illinois, United States
  • Giedrius Kalesnykas
    Experimentica ltd, Kuopio, Finland
  • Footnotes
    Commercial Relationships   Symantas Ragauskas, Experimentica ltd (E), Experimentica ltd (I); Agne Ziniauskaite, Experimentica ltd (E); Simon Kaja, Experimentica ltd (R), Experimentica ltd (P), Experimentica ltd (I), Experimentica ltd (F), Experimentica ltd (C), Experimentica ltd (S), K&P Scientific LLC (I), Loyola University Chicago (E); Giedrius Kalesnykas, Experimentica ltd (E), Experimentica ltd (I), Experimentica ltd (S)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3204. doi:
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      Symantas Ragauskas, Agne Ziniauskaite, Simon Kaja, Giedrius Kalesnykas; Neuroprotection of retinal ganglion cells via NMDA-dependent mechanism in the mouse non-arteritic anterior ischemic optic neuropathy (NAION) model. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3204.

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      © ARVO (1962-2015); The Authors (2016-present)

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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.

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