Resveratrol Inhibits Wound Healing and Lens Fibrosis: A Putative Candidate for Posterior Capsule Opacification Prevention

Purpose : Posterior capsule opacification (PCO) is a common complication of cataract surgery. In addition to improved surgical methods and IOL designs it is likely additional agents will be needed to improve patient outcomes. Presently no pharmacological agent is in clinical use to prevent PCO. Here we investigate the putative ability of resveratrol (RESV), a naturally occurring polyphenol, as a therapeutic agent. Methods : The human lens epithelial cell line FHL124, a human lens capsular bag model and central anterior epithelium were employed as experimental systems. Standard culture was in 5% FCS EMEM. 10ng/ml Transforming growth factor-2 (TGFβ2) was used to induce fibrotic changes. A scratch wound assay was used to measure cell migration and the patch assay employed to assess matrix contraction by FHL124 cells. Protein expression was assessed by immunocytochemistry and western blot and gene expression by QRT-PCR. In capsular bags, cell growth across the posterior lens capsule, capsular wrinkling and EMT were determined by image analysis. Results : In FHL124 cells, addition of 30 μM RESV significantly impeded cell migration in a wound healing assay. RESV significantly inhibited TGFβ2-induced expression of the myofibroblast marker alpha-smooth muscle actin (α-SMA) at both the message and protein level as well as significantly inhibiting matrix contraction induced by TGFβ2. In human capsular bags, 30 μM RESV significantly inhibited cell growth. TGFβ2-induced α-SMA expression and capsular wrinkling were also significantly inhibited by RESV treatment. RESV significantly supressed expression of TGFβ2-induced genes associated with fibrotic disease, including matrix metalloproteinase-2 in FHL124 cells, capsular bags and central anterior epithelium. Conclusions : RESV can counter PCO related physiological events in two human lens model systems. RESV therefore has the potential to be used as a candidate agent for the prevention of PCO, which in turn could benefit millions of cataract patients.