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Updated: Aug 11, 2026
Examination of Anatomical Features of Retinal Ganglion Cells Under N-methyl-D-aspartic Acid (NMDA)-induced Excitotoxicity
Published on: September 19, 2025
Pro-apoptotic role of c-Jun in NMDA-induced neurotoxicity in the rat retina
Yasunari Munemasa1, Ritsuko Ohtani-Kaneko, Yasushi Kitaoka
1Department of Ophthalmology, St. Marianna University School of Medicine, Kawasaki-shi, Kanagawa, Japan. munemasa@marianna-u.ac.jp
Abstract:
We examined the role of c-Jun on N-methyl-D-aspartate (NMDA)-induced neurotoxicity in the rat retina. An increase in c-Jun mRNA, c-Jun protein and phosphorylated c-Jun (p-c-Jun) levels in the retina was detected 3 hr after intravitreal injection of NMDA (20 nmol). These levels peaked after 12 hr, and then returned to their control levels by 24 hr. c-Jun and p-c-Jun immunoreactivities were observed in the retinal ganglion cell layer (RGCL), especially in retinal ganglion cells (RGCs), and in the inner nuclear layer (INL) 12 hr after NMDA injection, and terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL)-positive cells were immunopositive for c-Jun and p-c-Jun. A c-Jun antisense oligodeoxynucleotide (AS ODN), which was simultaneously injected with NMDA, penetrated the cells in the RGCL and the INL, suppressed the NMDA-induced increase in c-Jun and p-c-Jun protein levels and reduced the number of TUNEL-positive cells in the RGCL 12 hr after the injection. The protective effect of c-Jun AS ODN on the NMDA-treated retina was also shown by the RGCL cell count and measurement of the IPL thickness, as well as by quantitative real-time PCR analysis of Thy-1 mRNA 7 days after the injection. These results suggest that c-Jun synthesis and phosphorylation participate in NMDA-induced neuronal cell death.
Insights
The study shows that c-Jun plays a role in N-methyl-D-aspartate (NMDA)-induced retinal neurotoxicity. Inhibiting c-Jun synthesis with antisense oligodeoxynucleotides protected retinal cells from NMDA-induced death.
Area of Science:
- Neuroscience
- Retinal Biology
- Molecular Biology
Background:
- N-methyl-D-aspartate (NMDA) receptor activation can lead to excitotoxicity and neuronal cell death in the retina.
- The transcription factor c-Jun is involved in cellular stress responses and apoptosis.
Purpose of the Study:
- To investigate the role of c-Jun in NMDA-induced neurotoxicity in the rat retina.
- To determine if inhibiting c-Jun can protect retinal neurons from NMDA-induced damage.
Main Methods:
- Intravitreal injection of NMDA in rats.
- Measurement of c-Jun mRNA, protein, and phosphorylated protein levels.
- Immunohistochemistry to detect c-Jun and phosphorylated c-Jun.
- Terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) assay.
- Administration of c-Jun antisense oligodeoxynucleotide (AS ODN).
- Retinal ganglion cell layer (RGCL) cell counting and inner plexiform layer (IPL) thickness measurement.
- Quantitative real-time PCR for Thy-1 mRNA.
Main Results:
- NMDA injection increased c-Jun and phosphorylated c-Jun levels in the retina, particularly in retinal ganglion cells (RGCs) and the inner nuclear layer (INL).
- NMDA-induced cell death, as indicated by TUNEL staining, colocalized with c-Jun and phosphorylated c-Jun.
- Administration of c-Jun AS ODN suppressed NMDA-induced c-Jun expression and reduced neuronal cell death.
- c-Jun AS ODN treatment preserved RGCL cell count and IPL thickness, and normalized Thy-1 mRNA levels.
Conclusions:
- c-Jun synthesis and phosphorylation are involved in the mechanisms of NMDA-induced retinal neurotoxicity.
- Inhibition of c-Jun offers a potential therapeutic strategy to protect against NMDA-induced retinal damage.
