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J.A. Burke, K.–M. Zhang, J. Yang, T. Lin, B. Jackson, A. Oyejide, L. Wheeler; Oral Memantine Increases Rate of ERG Recovery in Rabbits Following an Acute Retinal Ischemic Insult Induced by Elevated IOP . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4660.
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Purpose: To evaluate the effects of a single oral dose of memantine (20 mg/kg) on retinal changes produced by an acute retinal ischemic insult in pigmented rabbits Methods: Twelve Dutch–belted rabbits weighing 2.5 kg were randomized to receive either a single oral dose of 20 mg/kg memantine (n=6) or 50 mg sugar (placebo, n=6) in a gelatin capsule. Two hours later, rabbits were anesthetized with isofluorane, and prepared for unilateral acute retinal ischemia by raising IOP in the OD eye by 120 mm Hg for 45 minutes. To accomplish this, a reservoir with PBS was suspended 65 inches above the eye and connected to a 30 gauge needle inserted through the cornea into the anterior chamber. A drop of topical anesthetic (proparacaine) was placed upon the cornea prior to needle insertion. Follow–up consisted of simultaneous bilateral single flash ERGs (0.001, 0.01, 1 cd.s/m2) and 30 Hz flicker (1 cd.s/m2) with the Espion® ColorDome® ganzfeld at Day_2, Week_1 and Month_1 following ischemic insult. Also at Month_1, bilateral color fundus photos, HRT of the optic nerve head and OCT radial scans of the fundus, were taken. Animals were anesthetized with ketamine and acepromazine for the follow–up measures. At month_6, eyes from 2 animals in the memantine group and 2 animals in the placebo group were prepared for histology (H&E). Data are expressed as % of control (ischemic eye / contralateral normal eye). Results: There was better preservation of ERG responses in animals receiving memantine, especially at Month_1: ERG B–wave amplitude % control responses @ 0.001 cd.s/m2 for placebo and memantine were 27 ± 10 vs 42 ± 14 @ Day_2; 29 ± 15 vs 34 ± 15 @ Week_1; and 41 ± 9 vs 81 ± 15 (p=0.04) @ Month_1; similar responses were obtained with the 0.01 cd.s/m2 and 1 cd.s/m2 flash intensities. Decreases in optic nerve head cup volume (HRT) and retinal thickness (OCT) were similar between groups: % of control responses for placebo and memantine for cup volume were 90 ± 8 and 92 ± 8, respectively, and for retinal thickness, the values were 85 ± 7 and 92 ± 4. The histological evaluation @ Month_6 showed less retinal cell degeneration in the memantine group compared with the placebo group. Conclusions: Oral memantine was neuroprotective in this model of acute retinal ischemia. The effect was evident at later follow–up time points as assessed by functional measures, but not by retinal imaging evaluating anatomical hallmarks.
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