LAUSR

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)‐&bgr; is a key factor in the induction of EMT in LECs. Although Rho kinase (ROCK) plays an important role in EMT induced by TGF‐&bgr;, it is unknown whether ROCK inhibition affects type I collagen expression in TGF‐&bgr;‐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‐&bgr;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 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 &agr;‐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‐&bgr; signaling in LECs by topical application of a ROCK inhibitor can prevent the formation of ASCs. HIGHLIGHTSY‐27632 decreased type I collagen expression in human LECs induced by TGF‐&bgr;.UVR‐B exposure induced anterior subcapsular opacities in mice.In these opacities, &agr;‐SMA and type I collagen were present around flattened LECs.Topical administration of Y‐27632 reduced anterior subcapsular cataracts formation.