Transcriptomic Analysis of Human Lens Epithelium Tissue With and Without Cataract Surgery: Uncovering Novel Pathways...

Cataract surgery is the most commonly performed ophthalmic procedure worldwide, yet long-term molecular adaptations of lens epithelial cells (LECs) following surgery remain poorly understood.

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 1690 upregulated and 579 downregulated genes. Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) identified activation of oxidative stress response, cell survival, and immune response signatures. Notably, genes involved in antioxidant defense (e.g. SOD2, GCLC, and TXN), anti-apoptotic regulation (BCL2L1 and XIAP), and DNA repair (ERCC1) were significantly upregulated in post-surgical samples. Immune-related genes (IL-8, CCL2, and TGFβ2) and complement components (C2 and C3) were elevated, suggesting persistent inflammatory signaling. Enrichment of TGF-β and Wnt/β-Catenin signaling, along with increased expression of epithelial mesenchymal transition (EMT) and fibrosis markers (ACTA2, FN1, and TNC), indicated long-term fibrotic remodeling. Senescence-associated genes (CDKN2A and CDKN1A) were also upregulated, whereas LMNB1 was downregulated, supporting a senescent phenotype in a subset of LECs. Immunofluorescence confirmed senescence and fibrosis at the protein level. GO enrichment and clustering revealed strong upregulation of cell migration, corroborated by elevated expression of migratory genes (ICAM1, VCAM1, and PLAU), suggesting acquisition of an invasive phenotype.

Our findings reveal that LECs undergo sustained molecular reprogramming after cataract surgery, including inflammatory, fibrotic, migratory, and senescent changes. These adaptations may contribute to posterior capsule opacification (PCO) and highlight therapeutic targets for its prevention.