Neuroprotective effect of the calcium channel blocker nilvadipine on retinal ganglion cell death in a mouse ocular hypertension model.

ABSTRACT

We investigated whether nilvadipine has a neuroprotective effect on retinal ganglion cells (RGCs) in a mouse model of ocular hypertension (OH) that expresses cyan fluorescein protein (CFP) in RGCs. OH was induced in the right eyes of Thy1-CFP transgenic mice using a laser. Nilvadipine or vehicle treatment began simultaneously with OH modeling and was administered intraperitoneally once daily for 8 weeks. Intraocular pressure (IOP) in both the laser- and non-treated eyes was measured weekly with the microneedle method, and calculations were performed to estimate the pressure insult in each eye. Using a retinal whole mount, the number of RGCs was counted at week 9. Laser-treated eyes showed a significant increase in IOP (p < 0.01), and the pressure insult did not differ between the drug-treated groups. Over time, laser treatment produced a significant decrease in the number of RGCs in the vehicle-treated groups, but this effect was attenuated by nilvadipine treatment. The pressure insult and RGC survival rate were significantly negatively correlated in the vehicle-treated group (y = -0.078 x + 107.8, r = 0.76, p < 0.001), but not in the nilvadipine-treated group (y = -0.015 x + 99.9, r = 0.43, p = 0.128). Nilvadipine was a potent neuroprotective agent for RGCs in our mouse model of OH and may have potential for protection against glaucoma. This model is useful as a screening tool for drugs with retinal protective effects.