Dysfunction in amino acid synthesis pathways: Potential biomarkers for early glaucoma detection

• Published in: Acta ophthalmologica (Oxford, England) England), 2025-01, Vol.103 (S284), p.n/a
• Main Authors: Andrés‐Blasco, Irene, Bisbal, M. Carmen MArtínez, Gallego‐Martínez, Alex, Tufanisco, Elena Bendala, Martinez, Francisco Cavas, Marabotto, Marina Botello, Martinez‐Mañez, Ramon, Durán, Maria Dolores Pinazo
• Format: Article
• Language: English
• Subjects: Amino acids; Biomarkers; Formic acid; Glaucoma; Leucine; Magnetic resonance spectroscopy; Metabolic disorders; Metabolites; NMR; Nuclear magnetic resonance; Phenylalanine; Spectrum analysis; Taurine; Tears; Tryptophan; Uridine
• ISSN: 1755-375X; 1755-3768
• DOI: 10.1111/aos.17108

Aims/Purpose: Amino acids have been proposed as preclinical biomarkers of the risk of developing neurodegenerative and metabolic diseases. We used proton nuclear magnetic resonance (1H‐NMR) in tears for the first time to investigate alterations in essential amino acids in patients with primary open‐angle glaucoma (POAG). Methods: We planned an analytical pilot case‐control study for 30 participants aged 40‐80 years, divided into: POAG group (n = 11) and control group (CG; n = 19). Tears were obtained from each eye using capillarity. The samples were studied using 1H‐NMR spectroscopy, acquiring one‐dimensional spectra for each sample, and assigning the peaks according to their chemical shift (profiling) and information from various databases. The data from the chemometric analysis are shown as mean and standard deviation. Results: A total of 40 metabolites were assigned based on their chemical shifts, multiplicity, and scalar coupling between J cores. Our multivariate model included 11 to discriminate between POAG and CG: phenylalanine, phenylacetate, leucine, taurine, glycine, urea, glucose, N‐acetylated compounds, unsaturated fatty acid, formic acid, and uridine. Thus, the most relevant metabolites were phenylalanine, phenylacetate, leucine, taurine, glycine, urea, and glucose, showing a significant reduction in concentration in the tears of the POAG group for phenylalanine, phenylacetate, leucine, N‐acetylated compounds, formic acid, and uridine, compared to the CG. Conclusions: Our results suggested that the alteration in phenylalanine, tyrosine, and tryptophan signaling pathways and their effects are associated with an increased risk for POAG. Their decrease in tears maybe considered a potential biomarker to identify patients in the early stages of glaucoma.