Short-term TGF beta 2 exposure mediates long-term changes in the human lens capsular bag

Purpose: To determine whether a brief exposure to human TGFß2 can induce long-term enhanced transdifferentiation and matrix wrinkling in an in vitro model for posterior capsule opacification (PCO). Methods: Human lens capsular bag preparations were maintained in 1.5ml of EMEM (5% CO2) and were exposed to 10ng/ml TGFß2 for the initial 1hr or 2 days of culture. Control paired bags were untreated. In some cases, CAT-152 (lerdelimumab; human anti-TGFß2 monoclonal antibody) was added to the medium (10µg/ml) following 2 days exposure to TGFß2. Control bags were exposed to TGFß2 alone. End-point analyses at 28 days for F-actin and alpha smooth muscle actin (αSMA; a transdifferentiation marker) were performed using immunocytochemistry and wrinkling was assessed by phase contrast microscopy. Quantification was achieved using image analysis and the data (Table 1) expressed in terms of arbitrary intensity units. Results: Exposure of capsular bags to TGFß2 for 1hr or 2 days significantly increased capsular wrinkling, altered F-actin organisation and significantly enhanced αSMA expression at day 28 in an exposure-dependent manner (Table 1). When treated with CAT-152 following the initial 2 days TGFß2 exposure, wrinkling and αSMA expression were significantly reduced compared with TGFß2 controls (Table 1). Table 1. Wrinkling and αSMA expression in matched capsular bags.