Aldose Reductase Inhibition Prevents Development of Posterior Capsular Opacification in an In Vivo Model of Cataract Surgery

Abstract

PurposeCataract surgery is a procedure by which the lens fiber cell mass is removed from its capsular bag and replaced with a synthetic intraocular lens. Postoperatively, remnant lens epithelial cells can undergo an aberrant wound healing response characterized by an epithelial-to-mesenchymal transition (EMT), leading to posterior capsular opacification (PCO). Aldose reductase (AR) inhibition has been shown to decrease EMT markers in cell culture models. In this study, we aim to demonstrate that AR inhibition can attenuate induction of EMT markers in an in vivo model of cataract surgery.MethodsA modified extracapsular lens extraction (ECLE) was performed on C57BL/6 wildtype, AR overexpression (AR-Tg), and AR knockout mice. Immunofluorescent staining for the myofibroblast marker α-smooth muscle actin (α-SMA), epithelial marker E-cadherin, and lens fiber cell markers αA-crystallin and Aquaporin 0 was used to characterize postoperative PCO. Quantitative reverse transcription PCR (qRT-PCR) was employed to quantify postoperative changes in α-SMA, vimentin, fibronectin, and E-cadherin. In a separate experiment, the AR inhibitor Sorbinil was applied postoperatively and qRT-PCR was used to assess changes in EMT markers.ResultsGenetic AR knockout reduced ECLE-induced upregulation of α-SMA and downregulation of E-cadherin. These immunofluorescent changes were mirrored quantitatively in changes in mRNA levels. Similarly, Sorbinil blocked characteristic postoperative EMT changes in AR-Tg mice. Interestingly, genetic AR knockout did not prevent postoperative induction of the lens fiber cell markers αA-crystallin and Aquaporin 0.ConclusionsAR inhibition prevents the postoperative changes in EMT markers characteristic of PCO yet preserves the postoperative induction of lens fiber cell markers.

Lens epithelial cells-induced pluripotent stem cells as a model to study epithelial-mesenchymal transition during posterior capsular opacification

“…Cadherins (E-, N-, P- and R-cadherin), a family of calcium-dependent cell adhesion molecules, share a high degree of structural similarity which undergo homophilic interactions to maintain cell-cell contacts at adherens junctions [36]. It has been shown in embryonic stages of double mutant mice that E− and N-cadherin play an essential role during lens vesicle separation [37] Our results support earlier results that E-cadherin plays a critical role in the lens development and that it lost after 5 days in wild type mice [38]. N-cadherin which is a marker for mesenchymal cells was present at the site of cell-cell contact.…”

Aspirin inhibits TGFβ2-induced epithelial to mesenchymal transition of lens epithelial cells: selective acetylation of K56 and K122 in histone H3

“…The control group received 25 mM SPB alone. Mice consumed 3. to immunofluorescence detection of α-SMA (1:100 dilution) and collagen type IV (1:100 dilution, Sigma, Cat# 9272), as previously described [43].…”

Research Progress of Drug Prophylaxis for Lens Capsule Opacification after Cataract Surgery

“…In addition to the change of cell shapes, the common EMT markers include α-smooth muscle actin (α-SMA), fibronectins, and vimentin, and the reduction of these markers showed that EMT was inhibited. Zukin et al [29] selected the aldose reductase (AR) transgenic mice as the AR overexpression model and found that AR overexpression could increase the level of α-SMA and fibronectins in mice LECs via real-time Polymerase Chain Reaction (PCR), which reflected that AR overexpression activated LECs' EMT. After adding AR inhibitor Sorbinil, they observed the decline in the level of α-SMA and fibronectins, which meant the EMT of LECs was inhibited.…”