Topical administration of a ROCK inhibitor prevents anterior subcapsular cataract induced by UV-B irradiation
Topical administration of a ROCK inhibitor prevents anterior subcapsular cataract induced by UV-B irradiation
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DOI：
10.1016/j.exer.2019.01.016
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发表时间：
2019-04-01
影响因子：
3.4
通讯作者：
Sanbe, Atsushi
中科院分区：
文献类型：
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作者：
Imaizumi, Toshiyasu;Kurosaka, Daijiro;Sanbe, Atsushi
前囊下白内障(ASCs)在晶状体上皮细胞(LECs)向间充质转化(EMT)过程中，细胞外基质(ECM)沉积，其主要成分为I型胶原，导致视功能下降。转化生长因子-β是诱导晶状体上皮细胞发生EMT的关键因素。虽然Rho激酶(ROCK)在转化生长因子-5诱导的内皮细胞转化中起重要作用，但目前尚不清楚ROCK抑制是否影响转化生长因子-β刺激的晶状体上皮细胞和ASC形成中I型胶原的表达。本研究采用体外培养的人晶状体上皮(HLE)-B3细胞和体内紫外线照射(UVR)-B诱导的小鼠白内障模型对此进行了研究。我们发现，转化生长因子-β2促进HLE-B3细胞I型胶原mRNA的表达；这一作用被ROCK抑制剂Y27632以剂量依赖的方式抑制。UVR-B辐射可引起小鼠ASC的形成。组织病理学检查显示，前囊下区晶状体上皮细胞呈扁平状、多层状，横断面呈梭形。免疫组织化学分析显示，这些扁平的晶状体上皮细胞周围存在α-平滑肌肌动蛋白和I型胶原；局部滴注Y-27632可减少这些混浊。这些发现表明，局部应用ROCK抑制剂抑制晶状体上皮细胞中的转化生长因子-β信号可以防止ASCs的形成。
The deposition of extracellular matrix (ECM)-which is mainly composed of type I collagen-in anterior subcapsular cataracts (ASCs) during epithelial-to-mesenchymal transition (EMT) of lens epithelial cells (LECs) decreases visual function. Transforming growth factor (TGF)-beta is a key factor in the induction of EMT in LECs. Although Rho kinase (ROCK) plays an important role in EMT induced by TGF-5, it is unknown whether ROCK inhibition affects type I collagen expression in TGF-beta-stimulated LECs and ASC formation. This was investigated in the present study both in vitro using human lens epithelium (HLE)-B3 cells and in vivo using mice with ultraviolet radiation (UVR)-B-induced cataracts. We found that TGF-beta 2 increased type I collagen mRNA expression in HLE-B3 cells; this was inhibited in a dose-dependent manner by treatment with the ROCK inhibitor Y27632. UVR-B exposure caused ASC formation in mice. A histopathological examination revealed that LECs in the anterior subcapsular area were flattened and multi-layered, and had a spindle shape in cross section. Immunohistochemical analysis revealed the presence of a-smooth muscle actin and type I collagen around these flattened LECs; these opacities were reduced by topical instillation of Y-27632. These findings suggest that suppression of TGF-beta signaling in LECs by topical application of a ROCK inhibitor can prevent the formation of ASCs.