Abstract
Purpose :
Retinal ganglion cell (RGC) degeneration leads to irreversible vision loss in various pathological conditions, such as glaucoma. Glutamate excitotoxicity via N-methyl-D-aspartate (NMDA) receptors plays a major role in RGC loss. This study aims to establish an animal model of NMDA-induced RGC injury and evaluate the protective effects of NMDA receptor antagonists memantine and MK801 in this model.
Methods :
Retinal damage was induced by intravitreal injection of NMDA (20mmol/L, 5 μL) in SD rats. Memantine, MK801, and vehicle control were injected intraperitoneally 1 hour prior to NMDA injection (n=18/group). Electroretinogram (ERG) and optical coherence tomography (OCT) were recorded before, and 2, 7, and 14 days after dosing. Survival RGC was stained with RBPMS antibody and counted in the flat whole-mount retina under a fluorescent microscope.
Results :
Compared to model control, the b-wave amplitude in the MK-801 group increased by 63.1% and 66.3% on Day 8 in dark adapted 3.0 and dark adapted 10.0 ERG, respectively. Retinal thickness measured by OCT in the model group was significantly lower than normal control on post-dosing days 3, 8, and 15. Compared to the model control, retinal thickness in the MK-801 group was increased by 27.8% and 40.5% on post-dosing days 8 and 15, respectively, while the retinal thickness of the memantine group was similar to the model control. Compared to normal control, the RGC density in the model control group was significantly reduced. Compared to model control, the density of RGC in MK-801 and memantine groups increased by 165.0% and 28.5%, respectively, on post-dosing day 15.
Conclusions :
Intraperitoneal injection of MK-801 effectively attenuated NMDA-induced retinal ganglion cell injury in SD rats.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.