Effect of the Notch signaling pathway on retinal ganglion cells and its neuroprotection in rats with acute ocular hypertension.

AIM

To explore the effect of the Notch signaling pathway on retinal ganglion cells (RGCs) and optic nerve in rats with acute ocular hypertension (OH).

METHODS

Totally 48 Sprague-Dawley (SD) rats were included, among which 36 rats were selected to establish acute OH models. OH rats received a single intravitreal injection of 2 µL phosphate buffered solution (PBS) and another group of OH rats received a single intravitreal injection of 10 µmol/L γ-secretase inhibitor (DAPT). Quantitative real-time polymerase chain reaction (qPCR) and Western blot assay were adopted to determine the mRNA level of Notch and the protein levels of Notch, Bcl-2, Bax, caspase-3, and growth-associated protein 43 (GAP-43). The RGC apoptosis conditions were assessed by TUNEL staining.

RESULTS

The OH rats and PBS-injected rats had increased expression levels of Notch1, Bax, caspase-3, and GAP-43, decreased expression levels of Bcl-2, and increased RGC apoptosis, with severer macular edema and RGCs more loosely aligned, when compared with the normal rats. The DAPT-treated rats displayed increased expression levels of Notch1, Bax, caspase-3, and GAP-43, decreased expression levels of Bcl-2, and increased RGC apoptosis, in comparison with the OH rats and PBS-injected rats. RGCs were hardly observed and macular edema became severe in the DAPT-treated rat.

CONCLUSION

The Notch signaling pathway may suppress the apoptosis of retinal ganglion cells and enhances the regeneration of the damaged optic nerves in rats with acute OH.