PRRX1 drives pericyte–endothelial cell crosstalk in pathological retinal angiogenesis via regulation of the IGFBP7–JAK1–STAT3 axis

Pathological angiogenesis is a hallmark of vision‑threatening retinal neovascular diseases, yet therapeutic options beyond anti-vascular endothelial growth factor treatments remain limited and often yield incomplete responses. This study identifies the transcription factor paired related homeobox 1 (PRRX1) as a pivotal regulator of pathological pericyte-endothelial cell crosstalk within the retinal neurovascular unit. Integrated single-cell and bulk RNA sequencing analyses identified a distinct pro‑angiogenic pericyte subpopulation characterized by PRRX1 expression, which engages in crosstalk with an endothelial cell subset enriched for insulin‑like growth factor binding protein 7 (IGFBP7). Chromatin immunoprecipitation sequencing and dual‑luciferase reporter assays confirmed that PRRX1 directly binds to the IGFBP7 promoter to drive its transcription. Functional validation through in vitro co-culture models and in vivo oxygen-induced retinopathy experiments demonstrated that the PRRX1-IGFBP7 axis drives endothelial JAK1-STAT3 activation, thereby promoting pathological angiogenesis. These findings delineate a novel transcriptional mechanism regulating pericyte–endothelial cell crosstalk and highlight the PRRX1–IGFBP7–JAK1–STAT3 axis as a promising therapeutic targe for promoting neurovascular unit stability in retinal neovascular diseases.