Abstract
Purpose :
Cataract renders millions blind throughout the world. Currently the only treatment for cataract is surgery, following which a high proportion of patients develop a secondary loss of vision, posterior capsule opacification (PCO). PCO results from a wound-healing response believed to be strongly influenced by the pro-fibrotic transforming growth factor-β (TGFβ). Strategies to prevent or retard PCO are required and pharmacological intervention remains an option. With this in mind, we investigated the potential of the naturally occurring polyphenol, resveratrol (RESV), to prevent cell proliferation, matrix contraction and EMT associated with PCO development.
Methods :
In vitro capsular bags were generated from human donor eyes by simulated cataract surgery, isolated by cutting of the zonules and secured to a 35mm tissue culture dish using entomological pins. Match-paired experiments were performed and culture took place in 5% FCS supplemented EMEM. In certain cases preparations were treated with RESV (30µM) and/or TGFβ2 (10ng/ml). Capsular bags were cultured for a 7 day period with experimental conditions replaced at day 4. Observations of cell coverage on the central posterior capsule (within the rhexis margin) were taken daily by phase-contrast microscopy. Immunocytochemistry was employed at end-point to assess the trans-differentiation marker, α-SMA. Image analysis was used to measure capsular wrinkling/matrix contraction.
Results :
TGFβ2 treatment induced a significant increase in α-SMA expression in cells present on the central posterior capsule and capsular wrinkling. TGFβ2 also appeared to inhibit the rate of cell growth across the posterior capsule. RESV significantly inhibited cell growth across the posterior capsule compared to untreated controls, whereas no significant changes in α-SMA expression or capsular wrinkling were observed at experimental end-point. Treatment with RESV in the presence of TGFβ2 resulted in significant retardation of cell growth across the posterior capsule, inhibition of α-SMA expression and suppression of capsular wrinkling at end-point.
Conclusions :
Resveratrol was found to significantly suppress cell growth across the posterior lens capsule as well as TGFβ2-induced EMT and matrix contraction. These events are associated with PCO following cataract surgery and thus resveratrol could serve as a useful agent for the therapeutic management of PCO.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.