Excessive Stretching Drives RPE Inflammation and ECM Remodeling in Ectopia Lentis Retinopathy

This study investigated the posterior segment manifestations and molecular mechanisms of retinopathy in ectopia lentis (EL) by subjecting retinal pigment epithelial (RPE) cells to excessive mechanical stretching. A total of 127 patients with EL and 149 healthy controls underwent comprehensive ophthalmic examinations. Aqueous humor from 10 patients per group underwent untargeted metabolomic analysis. In vitro, ARPE-19 cells were subjected to excessive mechanical stretching using a cell-tank device mimicking axial elongation. The results showed that patients with EL exhibited significantly longer Z-AL than controls, with 36.22% demonstrating retinal abnormalities. Metabolomic and RNA-seq analyses revealed enriched inflammatory metabolites and activated ECM-remodeling pathways. Real-time quantitative PCR (RT-qPCR), immunofluorescence (IF), Western blotting (WB), and an enzyme-linked immunosorbent assay (ELISA) confirmed elevated secretion of TNF-α, IL-6, and MMP3 in stretched RPE cells, consistent with the metabolomic findings. Excessive mechanical stretching induces inflammatory and ECM remodeling responses in RPE cells, potentially contributing to the retinopathy observed in EL. By integrating clinical, metabolomic, and transcriptomic data, this study highlights TNF-α, IL-6, and MMP3 as inflammatory mediators linking biomechanical stress to retinal abnormalities. These findings provide insights into disease-associated retinal remodeling in EL and may inform future therapeutic strategies.