Purpose:
Memantine is a non-competitive open channel blocker of N-methyl-D-aspartate (NMDA)-type glutamate receptors that blocks the channel at pathologically elevated glutamate concentrations but preserves normal channel function at physiological glutamate levels. Elevated glutamate concentrations have been suggested to cause neurodegenerative disorders including glaucoma and retinal disease. This study aims to provide electrophysiological data on the long-term functional effects of memantine on retinal degenerations in the DBA/2J (D2J) mouse.
Methods:
15 D2J mice received intraperitoneal injections of 5 mg/kg memantine twice a day on five days per week over a period of 8 months. Five untreated D2J mice and five C57Bl/6 (B6) mice served as controls. Measurements of intraocular pressure (IOP) and electroretinographical (ERG) recordings were performed at age 2, 6 and 10 months.
Results:
The IOPs were initially lower in the D2J mice compared to the B6 mice. But the IOPs increased more strongly in the D2J mice. There were no differences between treated and untreated D2J mice. The scotopic ERG responses were similar at the age of two months. With increasing age the response amplitudes decreased more strongly in the D2J mice than in the B6 mice. This decrease was smaller in treated animals especially in the b-wave amplitude. Photopic flicker ERG responses were already altered at the age of two months in D2J mice and were always similar in treated and untreated D2J animals.
Conclusions:
The IOPs were very similar to those reported previously in B6 and D2J mice. Memantine did not have influence on the measured IOP. The scotopic ERGs suggest a functionally protective effect of memantine at least at a post-receptoral level. The protective effect is not strong explaining failures in clinical studies. The photopic flicker ERG responses display a functional deficit already at a young age before memantine treatment. This implies that the photopic flicker ERG reveals a different degenerative mechanism in D2J mice independent of memantine treatment.
Keywords: electroretinography: non-clinical • degenerations/dystrophies • excitatory amino acid receptors