The Involvement of β-CateninCOX-2VEGF Axis in NMDA-Caused Retinopathy

Abstract EN

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.