Targeted Proteomics Profiling for Biomarker Discovery in Glaucoma Using the Olink Proteomics Platform

Metabolic
dysfunction plays a crucial role in the pathogenesis
of glaucoma. In this study, we used Olink proteomics profiling to
identify potential biomarkers for glaucoma. Aqueous humor samples
were obtained from 44 cataract patients and 44 glaucoma patients.
We identified 84 differentially expressed metabolic proteins between
the glaucoma and the cataract group. Gene Ontology enrichment analysis
highlighted the involvement of these proteins in ER-associated degradation
pathway, regulation of interleukin-13 production, and DNA damage response
pathway. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway
analysis further revealed links to pathways, such as tyrosine and
pyrimidine metabolism. Among these, ALDH1A1 emerged as a candidate
with a significant diagnostic potential for glaucoma. ALDH1A1 also
exhibited a prominent role in the protein–protein interaction
network. Elevated levels of ALDH1A1 in the aqueous humor of glaucoma
patients were confirmed both in clinical samples and in an ischemia/reperfusion
model. Functional assays confirmed that elevated ALDH1A1 induced retinal
ganglion cell (RGC) apoptosis in vitro and demonstrated
its pro-apoptotic role in RGCs in vivo. Collectively,
these findings not only underscore the significance of ALDH1A1 in
glaucoma but also provide valuable insights into clinical decision-making
and therapeutic strategies.