RNA-seq Analysis of Human Lens Capsules from Donors with and without Cataract Surgery History

Cataract surgery is the most commonly performed ophthalmic procedure worldwide, yet the long-term molecular adaptations of lens epithelial cells (LECs) following surgery remain poorly understood. In this study, we conducted bulk RNA sequencing on lens capsules from 34 human donors, including 17 with an average of 7 years post-cataract surgery and 17 non-cataract controls. Differential expression analysis revealed substantial transcriptional changes in post-surgical LECs, including 1,690 upregulated and 579 downregulated genes. Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) analyses identified activation of oxidative stress response, cell survival pathways, and immune response signatures. Collectively, our findings reveal that LECs undergo profound and sustained molecular reprogramming following cataract surgery, including inflammatory, fibrotic, migratory, and senescent changes. These adaptations may contribute to posterior capsule opacification (PCO) and highlight potential therapeutic targets for its prevention.