Olink Profiling of Aqueous Humor Identifies Novel Biomarkers for Wet Age-Related Macular Degeneration

Metabolic dysfunction is recognized as a contributing
factor in
the pathogenesis of wet age-related macular degeneration (wAMD). However,
the specific metabolism-related proteins implicated in wAMD remain
elusive. In this study, we assessed the expression profiles of 92
metabolism-related proteins in aqueous humor (AH) samples obtained
from 44 wAMD patients and 44 cataract control patients. Our findings
revealed significant alterations in the expression of 60 metabolism-related
proteins between the two groups. Notably, ANGPTL7 and METRNL displayed
promising diagnostic potential for wAMD, as evidenced by area under
the curve values of 0.88 and 0.85, respectively. Subsequent validation
studies confirmed the upregulation of ANGPTL7 and METRNL in the AH
of wAMD patients and in choroidal neovascularization (CNV) models.
Functional assays revealed that increased ANGPTL7 and METRNL played
a pro-angiogenic role in endothelial biology by promoting endothelial
cell proliferation, migration, tube formation, and spouting in vitro. Moreover, in vivo studies revealed
the pro-angiogenic effects of ANGPTL7 and METRNL in CNV formation.
In conclusion, our findings highlight the association between elevated
ANGPTL7 and METRNL levels and wAMD, suggesting their potential as
novel predictive and diagnostic biomarkers for this condition. These
results underscore the significance of ANGPTL7 and METRNL in the context
of wAMD pathogenesis and offer new avenues for future research and
therapeutic interventions.