resumo
Biofluid biomarkers of age-related macular degeneration (AMD) are still lacking, and their identification is challenging. Metabolomics is well-suited to address this need, and urine is a valuable accessible biofluid. This study aimed to characterize the urinary metabolomic signatures of patients with different stages of AMD and a control group (>50 years). It was a prospective, cross-sectional study, where subjects from two cohorts were included: 305 from Coimbra, Portugal (AMD patients n = 252; controls n = 53) and 194 from Boston, United States (AMD patients n = 147; controls n = 47). For all participants, we obtained color fundus photographs (for AMD staging) and fasting urine samples, which were analyzed using 1H nuclear magnetic resonance (NMR) spectroscopy. Our results revealed that in both cohorts, urinary metabolomic profiles differed mostly between controls and late AMD patients, but important differences were also found between controls and subjects with early AMD. Analysis of the metabolites responsible for these separations revealed that, even though distinct features were observed for each cohort, AMD was in general associated with depletion of excreted citrate and selected amino acids at some stage of the disease, suggesting enhanced energy requirements. In conclusion, NMR metabolomics enabled the identification of urinary signals of AMD and its severity stages, which might represent potential metabolomic biomarkers of the disease.
palavras-chave
SIGNATURES; SPECTROSCOPY; DISEASE; PLASMA; METABONOMICS; PREVALENCE; VALIDATION; DIAGNOSIS; REVEALS; CANCER
categoria
Biochemistry & Molecular Biology
autores
Lains, I; Duarte, D; Barros, AS; Martins, AS; Carneiro, TJ; Gil, JQ; Miller, JB; Marques, M; Mesquita, TS; Barreto, P; Kim, IK; Cachulo, MD; Vavvas, DG; Carreira, IM; Murta, JN; Silva, R; Miller, JW; Husain, D; Gil, AM
nossos autores
Ana Maria Pissarra Coelho Gil
Professor Associado com Agregação
Ana Sofia da Costa Martins
Estudante de doutoramento
António de Sousa Barros
Bolseiro de pós-Doutoramento
Daniela Duarte
Estudante de doutoramento
Tatiana João Ribeiro Gonçalves Carneiro
Estudante de doutoramentoProjectos
agradecimentos
This project was funded by the Fundacao para a Ciencia e a Tecnologia (FCT) (HMSP-ICJ/0006/2013), the Miller Retina Research Fund (MEE) and the Miller Champalimaud Award (MEE). This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, FCT ref. UID/CTM/50011/2019 and POCI-01-0145-FEDER-007679, financed by national funds through the FCT/MCTES. AMG and DD acknowledge the Portuguese National NMR Network (RNRMN), supported by FCT funds, and grant SFRH/BD/119509/2016.