Abstract
Purpose :
Posterior capsule opacification (PCO) is the most common complication after cataract surgery, which originated via a fibrotic process involving wound-healing and tissue remodeling initiated by traumatic injury during the surgical procedure. PCO is a multifactorial disease resulting from various factors and signaling pathways. However, a full-scale analysis of gene expression profile and pathways involved in lens epithelial cell (LEC) adaptation and transformation in human lens epithelium with or without cataract surgery history has never been performed. We recently performed a large-scale RNAseq study comparing 17 human lens epithelia from donors with a history of cataract surgery with 17 lens epithelia from healthy donors.
Methods :
17 lens capsules/epithelium from donors who have done cataract surgery (average ~5 years) and 17 healthy donors were collected. RNAseq was performed.
Results :
The principal component analysis (PCA) showed distinct clusters of donors with and without a history of cataract surgery. Differentially expressed genes (DEGs) analysis revealed 1,691 and 578 genes were up-and down-regulated more than 2-fold in the epithelium after surgery compared to no surgery control, respectively. We further conducted Gene Set Enrichment Analysis (GSEA) using MySigDB, a powerful gene enrichment tool using a pre-ranked gene database of all gene expression profiles in contrast to taking only significant DEGs. Several hallmark pathways with normalized enrichment scores >1.30 are enriched in the lens epithelium after cataract surgery, including active ROS and inflammatory responses. Intriguingly, TGFβ and Wnt/β-Catenin pathways are activated along with the EMT process.
Conclusions :
To our knowledge, this is the first comprehensive transcriptome analysis of a large cohort of human epithelium with and without cataract surgery, which is expected to provide much-needed information to decipher the mechanisms of PCO.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.