Topical administration of a ROCK inhibitor prevents anterior subcapsular cataract induced by UV-B irradiation.

Abstract

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)-β is a key factor in the induction of EMT in LECs. Although Rho kinase (ROCK) plays an important role in EMT induced by TGF-β, it is unknown whether ROCK inhibition affects type I collagen expression in TGF-β-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-β2 increased type I collagen mRNA expression in HLE-B3 cells; this was inhibited in a dose-dependent manner by treatment with the ROCK inhibitor Y-27632. 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 α-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-β signaling in LECs by topical application of a ROCK inhibitor can prevent the formation of ASCs.

• Authors: Toshiyasu Imaizumi, Daijiro Kurosaka, Umi Tanaka, Daisuke Sakai, Kazuhiro Fukuda, Atsushi Sanbe
• Journal: Experimental eye research (Exp Eye Res) Vol. 181 Pg. 145-149 (04 2019) ISSN: 1096-0007 [Electronic] England
• PMID: 30690025 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019. Published by Elsevier Ltd.

Chemical References

• ACTA2 protein, human
• Actins
• Amides
• Collagen Type I
• Enzyme Inhibitors
• Pyridines
• Y 27632
• rho-Associated Kinases

Topics

• Actins (metabolism)
• Amides (pharmacology)
• Cataract (drug therapy, metabolism)
• Cells, Cultured
• Collagen Type I (metabolism)
• Enzyme Inhibitors (pharmacology)
• Epithelial Cells (metabolism)
• Humans
• Lens Capsule, Crystalline (drug effects, metabolism)
• Pyridines (pharmacology)
• Ultraviolet Rays (adverse effects)
• rho-Associated Kinases (antagonists & inhibitors)