Effects of Memantine on the Multifocal ERG in Experimentally Glaucomatous Cynomolgus Monkeys

Abstract

Abstract: : Purpose:To determine the effect of memantine (M) treatment on retinal function in a nonhuman primate model of pressure–induced experimental glaucoma (ExpG). Methods:Pre– and multiple (1–4) post–treatment multifocal ERGs (mfERGs) were obtained in 9 cynomolgus monkeys. Intraocular pressure (IOP) was increased unilaterally by laser photocoagulation of the trabecular meshwork (LPTM) in all animals. M treatment (daily oral dose: 8 mg/kg) began 3–6 weeks before LPTM in 5 monkeys. At the end of testing, these animals had received M for 4–9 months. The remaining 4 ExpG animals received vehicle. The mfERG stimulus consisted of 241 equal–sized hexagons subtending ± 44 deg about the central visual axis. Mean luminance was 100 cd/m² and a standard 13.3–ms base period binary m–sequence was used. Animals were anesthetized with pentobarbital. Pupils were dilated. ERG–jet contact lens electrodes were referenced to subcutaneous needle electrodes at the ipsilateral outer canthi. The 1st–order kernel mfERG amplitude and implicit time, and oscillatory potentials (OP) and amplitude root mean squares (RMS) of the 1st– and 2nd–order kernels were averaged in 6 rings radiating from the foveal element. Separate repeated measures analyses of variance were applied to each mfERG primary wave (N1,P1,N2,P2), with retinal eccentricity, test day (pre– and post–LPTM), and treatment (M/vehicle) as factors. Results:In the M–treated animals, LPTM–eye IOPs at test ranged between 15–23 mm Hg pre–LPTM and between 15–51 mm Hg post–LPTM. Fellow eye IOP range was 13–23 mm Hg pre– and 12–23 mm Hg post–LPTM. Pre–LPTM c/d ratios (c/d) ranged between 0.2–0.3 OU. Post–LPTM c/d ranged between 0.0–0.9 in the lasered eye, with highest c/d observed at the later test days. ExpG delayed implicit times of all four 1st–order kernel mfERG waves. Additionally, ExpG reduced P2 wave amplitude. In contrast, ExpG resulted in larger OP and RMS amplitudes in the central retina. M–treated ExpG animals exhibited smaller delays for N1 and P1 waves compared to vehicle–treated ExpG animals. No effect of M on wave amplitude was evident. Conclusions:Implicit times of the 1st–order kernel mfERG waves are delayed in ExpG. M limited the extent of these delays. Amplitude measures were insensitive to the effects of M treatment. These preliminary results provide evidence that M treatment has some protective effects on the alterations in retinal function produced by ExpG.

Keywords: electroretinography: non–clinical