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Updated: Feb 18, 2026
Intravitreous Injection for Establishing Ocular Diseases Model
Published on: October 1, 2007
The Involvement of β-Catenin/COX-2/VEGF Axis in NMDA-Caused Retinopathy
Dan Ning1, Wei Kevin Zhang1, Han Tian1
1Department of Pharmacology, School of Pharmaceutical Sciences, South-Central University for Nationalities, No.182, Minyuan Road, Wuhan 430074, China.
Abstract:
NMDA, a molecule that is capable of producing the loss of retinal ganglia cells (RGCs), has been widely studied; however, the detailed mechanism is not yet clarified. Previously, Wnt/β-catenin signaling has been suggested to be involved in the NMDA-induced retinopathy. In addition, previous investigations in our group demonstrated the presence of a Wnt/β-catenin/COX-2 axis in dorsal root ganglions (DRGs). Therefore, here in this paper, we tested whether there is an association of such axis with NMDA-induced RGC loss. Rat retinal damage models generated by intravitreal injection of NMDA were used to measure the expression levels of β-catenin, COX-2, and VEGF in retinas, and the neuron numbers of the retinal GCL of rats were counted. Then, pharmacological tools (MK801, a NMDA receptor inhibitor; Dickkopf homolog 1, a specific inhibitor of the Wnt pathway; NS-398, a COX-2 inhibitor; and bevacizumab, IVB, a VEGF inhibitor) were introduced to evaluate the detailed roles of Wnt/β-catenin, COX-2, and VEGF in retinopathy of rats. Results demonstrated that all three factors in sequence are positively regulated neuronal loss induced by NMDA. These observations indicated that the Wnt pathway/COX-2/VEGF axis plays a pathogenic role in retinopathy and represented novel therapeutic targets.
Insights
N-methyl-D-aspartate (NMDA) triggers retinal ganglion cell (RGC) loss via a Wnt pathway/COX-2/VEGF axis. This pathway represents a novel therapeutic target for NMDA-induced retinopathy.
Area of Science:
- Neuroscience
- Ophthalmology
- Molecular Biology
Background:
- N-methyl-D-aspartate (NMDA) is known to cause retinal ganglion cell (RGC) loss, but the underlying mechanisms remain unclear.
- Wnt/β-catenin signaling has been implicated in NMDA-induced retinopathy, and a Wnt/β-catenin/COX-2 axis exists in dorsal root ganglions.
Purpose of the Study:
- To investigate the association between the Wnt/β-catenin/COX-2 axis and NMDA-induced RGC loss in a rat model.
- To elucidate the roles of Wnt/β-catenin, COX-2, and VEGF in NMDA-induced retinopathy.
Main Methods:
- Established rat models of retinal damage via intravitreal injection of NMDA.
- Measured retinal expression levels of β-catenin, COX-2, and VEGF.
- Quantified neuron numbers in the retinal ganglion cell layer (GCL).
- Utilized pharmacological inhibitors (MK801, Dickkopf homolog 1, NS-398, bevacizumab) to assess pathway involvement.
Main Results:
- NMDA injection led to increased expression of β-catenin, COX-2, and VEGF in rat retinas.
- All three factors (Wnt/β-catenin, COX-2, VEGF) were found to be sequentially regulated and positively correlated with NMDA-induced neuronal loss.
- Pharmacological inhibition of these factors mitigated NMDA-induced RGC loss.
Conclusions:
- The Wnt pathway/COX-2/VEGF axis plays a significant pathogenic role in NMDA-induced retinopathy.
- This axis represents a promising novel therapeutic target for treating NMDA-induced retinal damage.
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