Vitreous Olink Proteomics Uncovers Novel Inflammatory Proteins in Patients with Proliferative Diabetic Retinopathy

Mounting research indicates that an inflammatory environment is a key driver in the advancement of proliferative diabetic retinopathy (PDR). In this study, we analyze and contrast 92 inflammatory cytokine levels in the vitreous humor of individuals with PDR (<i>n</i> = 14) with those of control subjects diagnosed with idiopathic macular hole (IMH; <i>n</i> = 11), by using the Olink inflammation panel. Key findings revealed 22 differentially expressed proteins (DEPs) when comparing the PDR and IMH groups, with 21 proteins showing increased expression and only one demonstrating decreased levels. Among these DEPs, fibroblast growth factor 23 (FGF23) emerged as a particularly promising candidate, as elevated expression was observed in retinal tissue from both diabetic (db/db) mice and the high-glucose (HG) or glyoxal-treated Müller glia (MG) cultures. Functional studies demonstrated that the conditioned medium from HG-exposed MG significantly enhanced endothelial cell proliferation, migration, and tube formation. Importantly, this proangiogenic effect was markedly attenuated when FGF23 activity was blocked using a neutralizing antibody, suggesting its critical role in MG-mediated angiogenesis under hyperglycemic conditions. Collectively, the findings demonstrated that individuals with PDR exhibited elevated concentrations of multiple inflammatory cytokines. Additionally, FGF23 emerged as a promising new candidate for the targeted treatment of this condition.