Shandong University of Traditional Chinese Medicine, No. 48#, Yingxiongshan Road, Jinan, 250002, China.
Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, No. 48#, Yingxiongshan Road, Jinan, 250002, China.
Eur J Pharmacol. 2023 Dec 5;960:176111. doi: 10.1016/j.ejphar.2023.176111. Epub 2023 Oct 18.
Myopia is one of the most prevalent eye diseases that seriously threaten the eyesight of children and adolescents worldwide. However, the pathogenesis is still unclear, and effective drugs are still scarce. In the present study, the guinea pigs were randomly divided into a normal control (NC) group, a lens-induced myopia (LIM) group, a NOS inhibitor (L-NMMA) injection group, and a NOS inhibitor solvent phosphate-buffered saline (PBS) group and the animals received relevant treatments. After 2- and 4-week different treatments, we noted that the refraction and choroidal thickness in the LIM group decreased compared with the NC group, whereas the ocular axial length increased significantly, and the choroid showed a fibrotic trend. The expression of NOS1, NOS3, TGF-β1, COLI, and α-SMA at gene and protein levels was increased significantly in the choroid (all P < 0.05). After intravitreal injection of NOS inhibitor L-NMMA, we found that compared with the LIM group, the refraction and the choroidal thickness significantly increased, whereas the axial length reduced significantly, accompanied by an increase of choroidal thickness and an improvement of choroidal fibrosis. The expression levels of choroidal NOS1, NOS3, TGF-β, COLI, and α-SMA were significantly reduced (all P < 0.05). In conclusion, the trend of choroidal fibrosis in LIM guinea pigs is positively correlated with the increase in axial length. The NOS inhibitor L-NMMA can alleviate the process of choroidal fibrosis in myopic guinea pigs by inhibiting NO signaling pathway.
近视是一种最常见的眼部疾病,严重威胁着全世界儿童和青少年的视力。然而,其发病机制尚不清楚,有效的药物仍然稀缺。在本研究中,豚鼠被随机分为正常对照组(NC 组)、晶状体诱导性近视(LIM)组、一氧化氮合酶抑制剂(L-NMMA)注射组和一氧化氮合酶抑制剂溶剂磷酸盐缓冲液(PBS)组,并给予相应的处理。经过 2 周和 4 周的不同处理后,我们注意到 LIM 组的屈光度和脉络膜厚度较 NC 组降低,而眼轴明显增加,脉络膜呈纤维化趋势。NOS1、NOS3、TGF-β1、COLI 和α-SMA 的表达在基因和蛋白水平均明显增加(均 P<0.05)。玻璃体腔注射NOS 抑制剂 L-NMMA 后,我们发现与 LIM 组相比,屈光度和脉络膜厚度明显增加,而眼轴明显缩短,脉络膜厚度增加,脉络膜纤维化得到改善。脉络膜 NOS1、NOS3、TGF-β、COLI 和α-SMA 的表达水平明显降低(均 P<0.05)。综上所述,LIM 豚鼠脉络膜纤维化的趋势与眼轴的增加呈正相关。NOS 抑制剂 L-NMMA 通过抑制 NO 信号通路可以减轻近视豚鼠脉络膜纤维化的进程。