title: Influence of aldose reductase on epithelial-to-mesenchymal transition signaling in lens epithelial cells.
abstract: Cataract is the most frequent cause of blindness worldwide and is treated by surgical removal of the opaque lens to restore the light path to the retina. While cataract surgery is a safe procedure, some patients develop a complication of the surgery involving opacification and wrinkling of the posterior lens capsule. This process, called posterior capsule opacification (PCO), requires a second clinical treatment that can in turn lead to additional complications. Prevention of PCO is a current unmet need in the vision care enterprise. The pathogenesis of PCO involves the transition of lens epithelial cells to a mesenchymal phenotype, designated epithelial-to-mesenchymal transition (EMT). Our previous studies showed that transgenic mice designed for overexpression of human aldose reductase developed lens defects reminiscent of PCO. In the current study, we evaluated the impact of aldose reductase (AR) on expression of expression of EMT markers in the lens. Primary lens epithelial cells from AR-transgenic mice showed downregulated expression of Foxe3 and Pax6 and increased expression of α-SMA, fibronectin and snail, a pattern of gene expression typical of cells undergoing EMT. A role for AR in these changes was further confirmed when we observed that they could be normalized by treatment of cells with Sorbinil, an AR inhibitor. Smad-dependent and Smad-independent pathways are known to contribute to EMT. Interestingly, AR overexpression induced ERK but not Smad-2 activation. These results suggest that elevation of AR may lead to activation of ERK signaling and thus play a role in TGF-β/Smad independent induction of EMT in lens epithelial cells.
authors.affiliation: Department of Ophthalmology, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Kun-Che
authors.initials: KC
authors.lastname: Chang
authors.affiliation: Department of Ophthalmology, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Biehuoy
authors.initials: B
authors.lastname: Shieh
authors.affiliation: Department of Ophthalmology, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address: mark.petrash@ucdenver.edu.
authors.forename: J Mark
authors.initials: JM
authors.lastname: Petrash
mesh_terms: D000449:Aldehyde Reductase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D007908:Lens, Crystalline / Q000166:cytology; D051379:Mice; D000071841:PAX6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; D005353:Fibronectins; D051858:Forkhead Transcription Factors; C498612:Foxe3 protein, mouse; D000071841:PAX6 Transcription Factor; C000605732:Pax6 protein, mouse; D000071250:Snail Family Transcription Factors; D053781:Transforming Growth Factor beta2; D000449:Aldehyde Reductase; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Aldose reductase; EMT; ERK; PCO