Dynamic and differential regulation in the micro RNA expression in the developing and mature cataractous rat lens

Recent evidence supports a role for micro RNA s (mi RNA s) in regulating gene expression, and alterations in gene expression are known to affect cells involved in the development of ageing disorders. Using developing rat lens epithelial cells ( LEC s), we profiled the expression of mi RNA s by a microarray‐based approach. Few gene expression changes known to be involved in pathogenesis or cytoprotection were uniquely influenced by mi RNA expression. Most mi RNA s increased or decreased in abundance (let 7b, let 7c, miR29a, miR29c, miR126 and miR551b) in LEC s/lenses during late embryonic and post‐natal development and in cataract. Among them, miR29a, miR29c and miR126 were dramatically decreased in cataractous LEC s from Shumiya Cataract Rats ( SCR s). Specifically, the cytoskeleton remodelling genes tropomyosin (Tm) 1α and 2β, which have been implicated in the initiation of pathophysiology, were targets of miR29c and were over‐stimulated as demonstrated by inhibitor experiments. In transfection experiments, increasing the level of miR29c caused a corresponding decrease in the expression of Tm1α and 2β, suggesting that miR29c may regulate the translation of Tm1α and 2β. 3′ UTR luciferase activity of Tm1α, not 2β, was significantly decreased in miR29c‐transfected mouse LEC s. These findings demonstrate changes in mi RNA s expression, and target molecules have potential as diagnostic indicators of ageing and as a foundation of miR‐based therapeutics for age‐related diseases.