Inhibition of Rho kinase suppresses capsular contraction following lens injury in mice
Inhibition of Rho kinase suppresses capsular contraction following lens injury in mice
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DOI：
10.4103/tjo.tjo_80_19
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发表时间：
2020-04-01
影响因子：
1.1
通讯作者：
Saika, Shizuya
中科院分区：
文献类型：
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作者：
Ichikawa, Kana;Tanaka, Sai-Ichi;Saika, Shizuya
目得：我们研究了全身性盐酸法舒地尔和一种心肌素相关转录因子-A（MRTF-A）核转位抑制剂对小鼠穿刺损伤透镜囊膜收缩的影响。材料和方法：在全身和局部麻醉下，在全身性盐酸法舒地尔（腹膜内，10 mg/kg体重）或溶媒给药后1 h，雄性成年C57 Bl/6小鼠出现前囊破裂的透镜损伤。在滴注氧氟沙星软膏后，每天给予盐酸法舒地尔或溶媒，持续5天和10天，使小鼠愈合。在另一系列实验中，我们检查了全身施用MRTF-A抑制剂（CCG-203971，100 mg/kg，每天两次）对第5天或第10天损伤的透镜中的纤维化反应和组织收缩的影响。对眼睛进行组织学和免疫组织化学处理，以检测SM 22、增殖细胞核抗原（PCNA）或MRTF-A。在苏木精和伊红染色的样本中，测量前囊破裂的每个边缘之间的距离并进行统计学分析。结果：在第5天，邻近囊膜破裂边缘形成一簇透镜细胞聚集。它含有用SM 22和PCNA标记的细胞。在第5天，法舒地尔组小鼠的细胞簇的大小大于对照组小鼠。全身法舒地尔或CCG-203971在某些时间点抑制囊破裂的过度收缩。结论：盐酸法舒地尔全身给药可作为白内障-人工透镜手术后囊袋收缩的治疗策略。
PURPOSE: We investigated the effect of systemic fasudil hydrochloride and an inhibitor of nuclear translocation of myocardin-related transcription factor-A (MRTF-A) on capsular contraction in a puncture-injured lens in mice. MATERIALS AND METHODS: Lens injury of an anterior capsular break was achieved in male adult C57Bl/6 mice under general and topical anesthesia at 1 h after systemic fasudil hydrochloride (intraperitoneal, 10 mg/kg body weight) or vehicle administration. The mice were allowed to heal after instillation of ofloxacin ointment, for 5 and 10 days with daily administration of fasudil hydrochloride or vehicle. In another series of experiment, we examined the effect of systemic administration of an MRTF-A inhibitor (CCG-203971, 100 mg/kg twice a day) on fibrogenic reaction and tissue contraction in an injured lens on day 5 or 10. The eye was processed for histology and immunohistochemistry for SM22, proliferating cell nuclear antigen (PCNA), or MRTF-A. In hematoxylin and eosin -stained samples, the distance between each edge of the break of the anterior capsule was measured and statistically analyzed. RESULTS: A cluster of lens cell accumulation was formed adjacent to the edge of the capsular break on day 5. It contained cells labeled for SM22 and PCNA. The size of the cell cluster was larger in fasudil group of mice than in control mice on day 5. Systemic fasudil or CCG-203971 suppressed an excess contraction of the capsular break at certain time points. CONCLUSION: Systemic administration of fasudil hydrochloride could be a treatment strategy of postoperative capsular contraction following cataract-intraocular lens surgery.