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. Overall design: 34 lens capsules were used for bulk RNA sequencing (RNAseq), comprising 13 males and 4 females from non-cataract donors and 17 lens capsules from post-surgery cataract donors, consisting of 6 males and 11 females. The post-mortem interval (PMI) for tissue harvest ranged from 2 to 10 hours, with an average PMI of 7.5 hours for non-cataract individuals and 5.4 hours for post-cataract surgery individuals. The average age in the post-cataract group was higher, at 74.1 years, compared to 67.2 years for non-cataract individuals. After stratification by post-cataract surgery status, no significant differences were observed in age or sex. The average time since cataract surgery among donors in the post-cataract group was 7.0 years, with surgeries performed 2 to 14 years before sample collection.