Human lens epithelial cells induce the inflammatory response when placed into the lens capsular bag model of posterior capsular opacification.

Purpose: Cataracts are typically treated by phacoemulsification followed by intraocular lens implantation. Studies of mouse models of cataract surgery have revealed that lens epithelial cells rapidly remodel their transcriptome to express proinflammatory cytokines after lens fiber cell removal, but it is currently unknown whether this response is conserved in human lenses. This study seeks to fill this knowledge gap. Methods: Human cadaver eyes from 70 to 89 year old individuals were prepared for the human capsular bag model of cataract surgery. The central epithelium was preserved in RNAlater during culture preparation, then the equatorial epithelium was either immediately preserved in RNAlater after the culture was created, or 24 h later. Gene expression profiles were generated by bulk sequencing of RNA isolated from these tissue samples. The transcriptomic response of human cadaver-derived lens epithelial cells to culture in this "capsular bag" model was characterized by bioinformatic analysis. The human response was directly compared to that of 24-month-old mouse lens epithelial cells subjected to fiber cell removal surgery. Results: Human lens epithelial cells remodel approximately a third of their transcriptome by 24 h after surgery, and like mice, this response consists of induction of proinflammatory cytokine genes, upregulation of fibrotic markers and downregulation of genes controlling the lens epithelial phenotype. Conclusions: These observations demonstrate that humans and mice have similar responses to cataract surgery and support the use of mice to study the response of lens epithelial cells to cataract surgery, suggesting that identified injury response mechanisms can be leveraged to elucidate new approaches to improve the outcomes of cataract surgery.