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

Abstract

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 used as experimental systems. Standard culture was in 5% fetal calf serum Eagle's minimum essential medium; 10 ng/mL transforming growth factor-b2 (TGFb2) 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. RESULTS. In FHL124 cells, addition of 30 lM RESV significantly impeded cell migration in a wound-healing assay. RESV significantly inhibited TGFb2-induced expression of the myofibroblast marker alpha-smooth muscle actin (a-SMA) at both the message and protein levels, as well as significantly inhibiting matrix contraction induced by TGFb2. In human capsular bags, 30 lM RESV significantly inhibited cell growth. TGFb2-induced a-SMA expression and capsular wrinkling were also significantly inhibited by RESV treatment. RESV significantly suppressed expression of TGFb2-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.

Long Noncoding RNA NEAT1 Regulates TGF-β2-Induced Epithelial-Mesenchymal Transition of Lens Epithelial Cells through the miR-34a/Snail1 and miR-204/Zeb1 Pathways

“…Our findings identified that Snail1 and Zeb1 are involved in the pathogenesis of PCO. Additionally, it is known that TGF-β2-induced EMT plays a pivotal role in PCO progression [7,8,42]. We found that NEAT1 knockdown suppressed Snail1 expression induced by TGF-β2 and miR-34a overexpression enhanced these effects in primary HLECs.…”

“…Based on the results, we hypothesized NEAT1 contributes to the pathogenesis of PCO. The previous studies have revealed that TGF-β2 is a pivotal inducer of EMT-related changes in PCO [7][8][9][10]. Hence, we explored whether TGF-β2 induces downregulation of epithelial differentiation markers (i.e., E-cadherin) and upregulation of mesenchymal cell markers (i.e., fibronectin) in primary HLECs through a NEAT1-dependent mechanism.…”

“…TGF-β is a requirement for LECs to undergo EMT, which is known as a pivotal inducer of EMT-related changes in PCO [7,8]. Furthermore, TGF-β2 is the predominant isoform in the aqueous humor [9,10].…”

Posterior capsule opacification: What's in the bag?

“…Using this system growth, EMT and differentiation have been observed and thus epithelial explants are a tractable system for the study of PCO (Gordon-Thomson et al, 1998;Mansfield et al, 2004;McAvoy and Chamberlain, 1989). Explant cultures can also be established from human lenses (Maidment et al, 2004;Shu and Lovicu, 2017;Smith et al, 2019;Weatherbee et al, 2019). To date, growth, EMT, increased matrix production and contraction have been studied, but differentiation is yet to be observed.…”

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

“…Resveratrol, one of the natural polyphenols, has the function of inhibiting fibrosis and antioxidants. Smith et al [37] added 30 μmol/L resveratrol into human LECs in vitro, and the results of quantitative real-time PCR showed that resveratrol could decrease the level of not only EMT markers, α-SMA and fibronectins, but also TGF-β activator, matrix metalloproteinase (MMP) 2. is study explained that resveratrol was more likely to prevent lens capsule opacification via hindering LECs' EMT, but they did not observe and evaluate the effect of resveratrol on other intraocular tissue cells. While Resveratrol has been authorized to the market, it is usually used as a nutrient supplement to improve bone density and protect the cardiovascular system, and further research that elaborates its pharmacologic mechanism is still in need.…”