Thapsigargin coated intraocular lenses prevent lens cell growth on the capsular bag

Purpose: Posterior capsule opacification (PCO) is the most common complication of modern cataract surgery and arises from resilient lens cell growth. Using an in vitro human capsular bag model it was possible to investigate the ability of growth-inhibitor coated IOLs to prevent PCO. Methods: A sham cataract operation was performed on human donor eyes, including capsutorhexis, nuclear hydroexpression and removal of residual fibres by irrigation with aspiration. At this point an IOL was implanted. In some cases IOLs were coated with the hydrophobia growth-inhibitor thapsigargin (Tg) using immersion concentrations of 0.2, 2 and 20μM. The capsular bag was dissected free, pinned on a petri dish and incubated with unsupplemented EMEM. Ongoing observations were by phase-contrast microscopy and end-point analysis by immunohistochemistry. Results: In all controls, cells were observed growing on the posterior capsule within the first week of culture. However, capsular bags cultured in the presence of Tg-coated lOLs demonstrated retarded growth on the posterior capsule and anterior IOL surfaces. Coating concentrations of 20p,M Tg, not only prevented growth on the posterior capsule, but eventually resulted in a complete loss of viable cells. During the first week of culture, thapsigargin-induced degradation of the cytoskeletal components, actin and vimentin, was observed in a small number of cells. At later stages of culture (-14 days) the majority of cells exhibited similar cytoskeletal degradation. Conclusions: Using a human capsular bag model which closely mimics the clinical situation, thapsigagin coated lOLs (>2(iM) were shown to be effective at preventing lens cell growth on the caosular bag. Thaosiearein coating of the IOL provides a promising strategy to eliminate PCO.