A novel ocular fibrosis signature for AMD using transcriptomic profiling of the two-stage laser-induced subretinal fibrosis mouse model.

Using RNA-seq on RPE/Choroid from a two-stage laser-induced subretinal fibrosis mouse model, we identified a novel core ocular fibrosis signature of 88 persistently upregulated genes across acute-to-chronic phases (days 3–10 post-injury).

This signature, enriched in epithelial-mesenchymal transition, complement activation, and inflammatory pathways, showed choroid-specific expression with minimal retinal involvement. Cross-validation in independent chronic mouse data and multiple human AMD datasets (peripheral retina, surgically extracted CNV membranes, and macular RPE/choroid) confirmed progressive enrichment in advanced disease stages. Immunofluorescence in human fibrotic tissue validated key genes (Tenascin C, Tissue Inhibitor of Metalloproteinases-1, and Apelin receptor) with co-localization to myofibroblast-like cells and microglia.