Drug combination of topical ripasudil and brimonidine enhances neuroprotection in a mouse model of optic nerve injury

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY Journal of pharmacological sciences Pub Date : 2024-02-29 DOI:10.1016/j.jphs.2024.02.011

Kazuhiko Namekata , Takahiko Noro , Euido Nishijima , Akiko Sotozono , Xiaoli Guo , Chikako Harada , Youichi Shinozaki , Yoshinori Mitamura , Tadashi Nakano , Takayuki Harada

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Abstract

Purpose

To determine whether combination of topical ripasudil and brimonidine has more effective neuroprotection on retinal ganglion cells (RGCs) following injury to axons composing the optic nerve.

Methods

Topical ripasudil, brimonidine, or mixture of both drugs were administered to adult mice after optic nerve injury (ONI). The influence of drug conditions on RGC health were evaluated by the quantifications of surviving RGCs, phosphorylated p38 mitogen-activated protein kinase (phospho-p38), and expressions of trophic factors and proinflammatory mediators in the retina.

Results

Topical ripasudil and brimonidine suppressed ONI-induced RGC death respectively, and mixture of both drugs further stimulated RGC survival. Topical ripasudil and brimonidine suppressed ONI-induced phospho-p38 in the whole retina. In addition, topical ripasudil suppressed expression levels of TNFα, IL-1β and monocyte chemotactic protein-1 (MCP-1), whereas topical brimonidine increased the expression level of basic fibroblast growth factor (bFGF).

Conclusions

Combination of topical ripasudil and brimonidine may enhance RGC protection by modulating multiple signaling pathways in the retina.

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局部用瑞帕舒地尔和溴莫尼定联合用药可增强小鼠视神经损伤模型的神经保护作用

目的是确定在构成视神经的轴突损伤后，外用瑞帕素地尔和溴莫尼定是否能更有效地保护视网膜神经节细胞（RGC）。对视神经损伤（ONI）后的成年小鼠分别给予局部利帕地尔、溴莫尼定或两种药物的混合物。通过量化视网膜中存活的RGC、磷酸化p38丝裂原活化蛋白激酶（phospho-p38）以及营养因子和促炎介质的表达，评估了药物条件对RGC健康的影响。局部用药利帕地尔和溴莫尼定分别抑制了ONI诱导的RGC死亡，而这两种药物的混合物进一步刺激了RGC的存活。局部用药利帕斯地尔和溴莫尼定抑制了ONI在整个视网膜中诱导的磷酸化p38。此外，局部用药利帕苏地尔抑制了 TNFα、IL-1β 和单核细胞趋化蛋白-1（MCP-1）的表达水平，而局部用药溴莫尼定则增加了碱性成纤维细胞生长因子（bFGF）的表达水平。通过调节视网膜中的多种信号通路，局部使用利帕地尔和溴莫尼定可能会增强对RGC的保护。

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来源期刊

Journal of pharmacological sciences 医学-药学

CiteScore

6.20

自引率

2.90%

发文量

104

审稿时长

31 days

期刊介绍： Journal of Pharmacological Sciences (JPS) is an international open access journal intended for the advancement of pharmacological sciences in the world. The Journal welcomes submissions in all fields of experimental and clinical pharmacology, including neuroscience, and biochemical, cellular, and molecular pharmacology for publication as Reviews, Full Papers or Short Communications. Short Communications are short research article intended to provide novel and exciting pharmacological findings. Manuscripts concerning descriptive case reports, pharmacokinetic and pharmacodynamic studies without pharmacological mechanism and dose-response determinations are not acceptable and will be rejected without peer review. The ethnopharmacological studies are also out of the scope of this journal. Furthermore, JPS does not publish work on the actions of biological extracts unknown chemical composition.