PRRX1 Orchestrates Pericyte-Myofibroblast Transition in Pathological Retinal Fibrosis.

PURPOSE: To investigate the role of PRRX1 in pericyte-myofibroblast transition and its contribution to pathological retinal fibrosis.

METHODS

Transcriptomic profiling was conducted on human fibrovascular membranes and murine oxygen-induced retinopathy retinas to assess PRRX1 expression and its association with fibrosis-related genes. Single‑cell RNA sequencing was performed on retinal tissues to identify pericyte subpopulations and characterize PRRX1-driven molecular pathways. In vitro, primary mouse retinal pericytes underwent hypoxia with or without small interfering RNA-mediated PRRX1 knockdown to assess fibrotic gene expression and cell migration. In vivo, a laser-induced choroidal neovascularization model was used to assess the effect of PRRX1 silencing on subretinal fibrosis.

RESULTS

PRRX1 was significantly upregulated in both human fibrovascular membranes and oxygen-induced retinopathy retinas; single‑cell RNA sequencing revealed its enrichment in pericyte subpopulations undergoing pericyte-myofibroblast transition. PRRX1 knockdown reduced fibrotic gene expression and migratory activity in primary pericytes under hypoxia. In the choroidal neovascularization model, PRRX1 silencing significantly reduced subretinal fibrosis and neovascular lesion area.

CONCLUSIONS

PRRX1 is a key regulator of pericyte-mediated fibrotic remodeling in the retina. Targeting PRRX1 offers a potential therapeutic approach for retinal fibrosis.