Gene expression and discovery during lens regeneration in mouse:regulation of epithelial to mesenchymal transition and lensdifferentiation

[摘要] Purpose: It has been shown that after extracapsular lens removal byanterior capsulotomy in the mouse, the lens can be regenerated. However,as the capsular bag is filled with fibers, epithelial to mesenchymaltransition (EMT), an event which is common after cataract surgery aswell, takes place during early stages. This study, using a unique mousemodel, was undertaken to identify novel regulators and networks in orderto more clearly understand secondary cataracts at the molecular level.Methods: We examined global gene expression via microarray analysisof mouse lens regeneration after extracapsular surgery. Gene expressionat different times after surgery was correlated with the processes ofEMT, which is seen in the initial stages of regeneration, and lens fiberdifferentiation, which occurs later.Results: Several notable patterns were observed from the geneclustering data. It was obvious from the analysis that initially thereis a response to injury, extensive matrix remodeling, and severedownregulation of genes encoding lens structural proteins. The patternsreturned gradually to normal three weeks after surgery. New genes wereidentified from the clustering results that might be potentialregulators of EMT and lens differentiation.Conclusions: With this approach, we demonstrated the utility of amouse model to study secondary cataracts at the molecular level.Extension of these studies in mice with known mutations affecting EMT orlens differentiation should allow the identification of the crucialmolecular players that could lead to better treatments of secondarycataracts.

[学科分类] 生物化学/生物物理