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Xingjun Fan, Zongbo Wei, Hong Yan; ROS-mediated Wnt/β-catenin signaling in lens epithelial cells adaptation and posterior capsule opacification. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1124.
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The PCO initiation and progression have similar pathogenesis as tissue fibrosis, and LECs hyperproliferation, transformation, and migration are often regulated by similar signaling pathways as tumorigenesis and tumor progression, such as epithelial-mesenchymal transition (EMT), which has been considered a critical process to regulate LECs fibrotic process and PCO formation. LECs after cataract surgery face a hostile growth microenvironment compared to healthy cells and the sustained stimulation from the microenvironment is expected to play a pivotal role in cell adaptation, survival, and invasion. We have discovered that the ROS-mediated Wnt/β-catenin signaling pathway is playing an important role in LECs adaptation and fibrosis (Am. J. Path, 2017). Now, we are testing this concept using rabbit PCO model with intraocular lens (IOL) implantation.
3 months old New Zealand albino rabbits were used for this study. Five groups of rabbits (8 rabbits/group/time point) were used to carry out a longitudinal study for 5-time points, i.e., at 0, 5day, 1m, 3m, and 6m. Unilateral (right eye) phacoemulsification-based (Phaco) cataract surgery was performed for all rabbits with an Alcon Acrysof SA60AT IOL implantation. The lens capsular image was collected twice per month, and the inflammatory markers, canonical Wnt/β-catenin, and TGFβ signaling, and redox status were determined by immunoblot, immunohistochemistry, and other biological analysis.
Elevated oxidation was detected from day 5 postoperatively, and a sustained oxidative stressed environment was observed in the entire course of this study. Various inflammatory cytokines including TGFβ1 and TGFβ2 were significantly increased at the day 5 postoperatively, then normalized relative to baseline. Intriguingly, a sustained Wnt/b-catenin signaling was seen up to 6 months after surgery. This is associated with elevated aSMA, vimentin, fibronectin, collagen I expression, and progressive posterior capsule opacification development. This study points to a critical role of Wnt/β-catenin singling pathway in the pathogenesis of PCO formation, particularly at chronic stage.
These results imply that survival signaling pathways are involved in oxidative stress adaptive response and may play a critical role in residual epithelial cells transdifferentiation after cataract surgery.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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