High-sensitivity vitreous proteomic analyses reveal involvement of IL-10/JAK-STAT signaling in the proliferative changes of retinopathy of prematurity.

Retinopathy of prematurity (ROP) is characterized by pathological retinal neovascularization and fibrovascular proliferation that may lead to retinal detachment and severe visual impairment. Although vascular endothelial growth factor (VEGF) is central to ROP pathogenesis, the molecular pathways associated with fibrovascular proliferation remain incompletely understood. Vitreous samples were collected intraoperatively from infants with stage 4 A-5 ROP and classified according to the extent of fibrovascular proliferation as mild (< 180°, n = 18) or severe (≥ 180°, n = 18). Vitreous samples from congenital cataract served as controls (n = 4). Proteomic profiling was performed using the Olink® Flex Panel based on proximity extension assay technology. Differential protein expression, hierarchical clustering, and pathway analyses were conducted. Multiple inflammatory, angiogenic, and immune-regulatory proteins demonstrated stepwise increases with worsening proliferative severity. Correlation analyses further showed significant associations between fibrovascular proliferation extent and vitreous concentrations of inflammatory and angiogenic mediators, including IL-10, IL-6, TNF, CXCL12, PGF, and TGFB1. Pathway analyses demonstrated enrichment of IL-10-mediated and JAK-STAT- signaling pathways associated with proliferative severity, suggesting that inflammatory signaling pathways may contribute alongside VEGF-related pathways in ROP.