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

• Published in: Investigative ophthalmology & visual science Vol. 60; no. 12; pp. 3863 - 3877
• Main Authors: Smith, Andrew J O, Eldred, Julie A, Wormstone, I Michael
• Format: Journal Article
• Language: English
• Published: United States 03-09-2019
• Subjects: Actins - metabolism; Antioxidants - pharmacology; Biomarkers - metabolism; Blotting, Western; Capsule Opacification - metabolism; Capsule Opacification - pathology; Capsule Opacification - prevention & control; Cell Line; Cell Movement - drug effects; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelial-Mesenchymal Transition - drug effects; Fibrosis - prevention & control; Humans; Immunohistochemistry; Lens Capsule, Crystalline - drug effects; Lens Capsule, Crystalline - metabolism; Lens, Crystalline - drug effects; Lens, Crystalline - pathology; Models, Biological; Posterior Capsule of the Lens - drug effects; Real-Time Polymerase Chain Reaction; Resveratrol - pharmacology; Transforming Growth Factor beta2 - pharmacology; Wound Healing - drug effects
• ISSN: 1552-5783; 1552-5783
• DOI: 10.1167/iovs.18-26248

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.
The human lens epithelial cell line FHL124, a human lens capsular bag model, and central anterior epithelium were used as experimental systems. Standard culture was in 5% fetal calf serum Eagle's minimum essential medium; 10 ng/mL transforming growth factor-β2 (TGFβ2) was used to induce fibrotic changes. A scratch wound assay was used to measure cell migration and the patch assay was used to assess matrix contraction by FHL124 cells. Protein expression was assessed by immunocytochemistry and Western blot and gene expression by quantitative RT-PCR. In capsular bags, cell growth across the posterior lens capsule, capsular wrinkling, and epithelial-to-mesenchymal transition were determined by image analysis.
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 levels, 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 suppressed expression of TGFβ2-induced genes associated with fibrotic disease, including matrix metalloproteinase-2 in FHL124 cells, capsular bags, and central anterior epithelium.
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.