Tsuruga Hidekazu, Murata Hiroshi, Araie Makoto, Aihara Makoto
Department of Ophthalmology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
Heliyon. 2023 Feb 16;9(3):e13812. doi: 10.1016/j.heliyon.2023.e13812. eCollection 2023 Mar.
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.
我们研究了尼伐地平在眼压升高（OH）小鼠模型中对视网膜神经节细胞（RGCs）是否具有神经保护作用，该模型中RGCs表达青色荧光蛋白（CFP）。使用激光诱导Thy1-CFP转基因小鼠右眼发生OH。尼伐地平或赋形剂处理在OH建模同时开始，每天腹腔注射1次，持续8周。每周用微针法测量激光治疗眼和未治疗眼的眼压，并进行计算以估计每只眼的压力损伤。在第9周时，使用视网膜全层铺片计数RGCs的数量。激光治疗眼的眼压显著升高（p < 0.01），药物治疗组之间的压力损伤无差异。随着时间的推移，激光治疗使赋形剂处理组的RGCs数量显著减少，但尼伐地平处理减弱了这种作用。在赋形剂处理组中，压力损伤与RGC存活率显著负相关（y = -0.078x + 107.8，r = 0.76，p < 0.001），但在尼伐地平处理组中无相关性（y = -0.015x + 99.9，r = 0.43，p = 0.128）。在我们的OH小鼠模型中，尼伐地平是一种有效的RGCs神经保护剂，可能具有预防青光眼的潜力。该模型可作为筛选具有视网膜保护作用药物的有用工具。
