Modeling Cataract Surgery in Mice

Our lab studies the molecular mechanisms underlying posterior capsular opacification, which is the most prevalent negative sequela of cataract surgery. This method has really given us some new fundamental insight into the response of remnant lens epithelial cells to cataract surgery. We found for the very first time that lens epithelial cells produce pro-inflammatory cytokines a day or two before any TGF-beta signaling and the expression of fibrotic genes.

And we've taken this even further to show that the expression of alpha-v beta-8 integrin on lens epithelial cells is required for the activation of TGF-beta, leading to later capsular bag fibrosis. And we've taken this even further to show that drugs that block alpha-v beta-8 integrin function block this pathway and prevent the fibrosis, suggesting that this is a new therapeutic target to prevent fibrotic PCO. PCO pathogenesis studies often focus on lens epithelial cell conversion to myofibroblasts via exogenous active TGF-beta.

However, this doesn't address how surgery triggers the fibrotic response. This in vivo model allows one to follow how lens epithelial cells respond to injury within the ocular environment, revealing both cell autonomous and non-autonomous mechanisms. We provide a unique in vivo technique for studying lens epithelial cell response to surgery while utilizing advanced genetic tools.

In the long term, investigations can elucidate likely therapeutic targets for inflammatory management, while leveraging our finding that alpha-v beta-8 integrin is a likely molecular target to prevent myofibroblast formation post-cataract surgery.