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 (n = 14) with those of control subjects diagnosed with idiopathic macular
hole (IMH; n = 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.