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. 2023 Feb 16;9(3):e13812.
doi: 10.1016/j.heliyon.2023.e13812. eCollection 2023 Mar.

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

Hidekazu Tsuruga  1 , Hiroshi Murata  1 , Makoto Araie  1 , Makoto Aihara  1
Affiliations

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

Hidekazu Tsuruga et al. Heliyon. .

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.

Keywords: Calcium channel blocker; Glaucoma; Mouse; Neuroprotection; Nilvadipine.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Changes of mouse body weight. Data are mean ± SD. There was no significant difference between vehicle and nilvadipine-treated mice during the study period.
Fig. 2
Fig. 2
Time course of average intraocular pressure (IOP) in the laser- and non-treated eyes. Data are mean ± SD. Vehicle group (a). Nilvadipine group (b). Laser-treated eyes had significantly higher IOP than non-treated eyes in both the vehicle and nilvadipine groups.
Fig. 3
Fig. 3
Regression analysis of the pressure insult and retinal ganglion cell (RGC) survival rate in the vehicle group. Regression analysis of whole (a), central (b), middle (c), and peripheral (d) retinal areas in the vehicle group. Linear regression analysis showed a significant negative correlation between the pressure insult and RGC survival rate (whole retina: r = 0.76, p < 0.001; central; r = 0.71, p < 0.001; middle; r = 0.78, p < 0.001; peripheral; r = 0.71, p < 0.001).
Fig. 4
Fig. 4
Regression analysis of the pressure insult and retinal ganglion cell (RGC) survival rate in the nilvadipine group. Regression analysis of whole (a), central (b), middle (c), and peripheral (d) retinal areas in the nilvadipine group. Linear regression analysis showed no significant correlation between the pressure insult and RGC survival rate (whole retina: r = 0.43, p = 0.128; central; r = 0.40, p = 0.154; middle; r = 0.34, p = 0.228; peripheral; r = 0.26, p = 0.370).
Fig. 5
Fig. 5
Retinal images of the pressure insult in laser-treated eyes. Representative retinal images of central (a), middle (b), peripheral (c), and whole (g) areas of laser-treated eyes in the vehicle group. Representative retinal images of central (d), middle (e), peripheral (f), and whole (h) areas of laser-treated eyes in the nilvadipine groups.
See this image and copyright information in PMC

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