Glypican-1 modulates TGF-β signaling to drive subretinal fibrosis through a non-canonical AKT-Cyclin A2 cell cycle axis and its inhibition alleviates fibrosis progression

Here, using unbiased proteomic profiling of aqueous humor samples from patients with nAMD together with transcriptomic analysis of human choroidal neovascular membranes, we performed cross-omics integration and identified glypican-1 (GPC1) as the only overlapping candidate that was markedly elevated in the aqueous humor of patients with SRF.

ELISA validation confirmed significantly increased GPC1 levels in the aqueous humor of patients with SRF, and experimental analyses localized GPC1 expression to retinal pigment epithelial (RPE) cells in vivo. GPC1 expression was markedly upregulated in fibrosis-induced human retinal pigment epithelial cells (ARPE-19) and in mouse models of SRF. Gain- and loss-of-function studies demonstrated that GPC1 promotes fibrotic responses in vitro and in vivo.