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Updated: Aug 19, 2026
Examination of Anatomical Features of Retinal Ganglion Cells Under N-methyl-D-aspartic Acid (NMDA)-induced Excitotoxicity
Published on: September 19, 2025
Effects of poly(ADP-ribose) polymerase inhibitor on NMDA-induced retinal injury
Hidehiro Oku1, Wakana Goto, Takashi Okuno
1Department of Ophthalmology, Osaka Medical College, Osaka, Japan. hidehirooku@aol.com
Purpose:
Excessive activation of poly(ADP-ribose) polymerase (PARP), a nuclear enzyme that is activated by DNA damage, leads to neuronal cell death through depletion of ATP. The purpose of this study was to determine whether inhibition of PARP has some neuroprotective effects on the N-methyl-D-aspartate (NMDA)-induced functional and morphological injury to the rabbit retina.
Methods:
Visually evoked potentials (VEPs) were recorded at different times after an intravitreal injection of NMDA (200, 660, and 2000 nmol) alone, or NMDA with 3-aminobenzamide (ABA, 200 nmol), a PARP inhibitor, or with MK-801 (200 nmol), an NMDA antagonist. The physiological changes were followed for 2 weeks, after which the eyes were enuculeated and prepared for histological examinations.
Results:
Intravitreal injections of NMDA reduced the amplitudes of rabbit VEPs and the number of cells in the retinal ganglion cell layer in a dose-dependent manner. No significant changes could be detected in the bright-flash electroretinograms (ERGs). Simultaneous injection of MK-801 (200 nmol) significantly diminished the changes induced by intravitreal NMDA. 3-Aminobenzamide (ABA) (200 nmol) also suppressed these changes, but its effects were less than those of MK-801.
Conclusions:
NMDA-induced retinal damage can be detected by VEPs, and PARP inhibition has some neuroprotective effects on the NMDA-induced retinal damage.
Insights
Poly(ADP-ribose) polymerase (PARP) inhibition shows neuroprotective effects against N-methyl-D-aspartate (NMDA)-induced retinal damage in rabbits. This damage, detectable by visually evoked potentials (VEPs), was lessened by PARP inhibition, suggesting a therapeutic potential.
Area of Science:
- Neuroscience
- Ophthalmology
- Biochemistry
Background:
- Poly(ADP-ribose) polymerase (PARP) activation by DNA damage can cause neuronal cell death via ATP depletion.
- N-methyl-D-aspartate (NMDA) receptor overactivation is implicated in retinal injury.
Purpose of the Study:
- To investigate the neuroprotective potential of PARP inhibition against NMDA-induced retinal damage in a rabbit model.
- To assess functional and morphological changes in the retina following NMDA exposure and PARP inhibition.
Main Methods:
- Rabbits received intravitreal injections of NMDA alone, or with the PARP inhibitor 3-aminobenzamide (ABA) or the NMDA antagonist MK-801.
- Visually evoked potentials (VEPs) were recorded, and histological examinations were performed after 2 weeks.
Main Results:
- NMDA injection dose-dependently reduced VEP amplitudes and retinal ganglion cell counts.
- MK-801 significantly attenuated NMDA-induced retinal damage.
- ABA also suppressed NMDA-induced damage, though to a lesser extent than MK-801.
Conclusions:
- Visually evoked potentials (VEPs) are effective in detecting NMDA-induced retinal damage.
- PARP inhibition demonstrates neuroprotective effects in NMDA-induced retinal injury, indicating potential therapeutic applications.