In developed countries, age-related macular degeneration is the leading cause of blindness. Some experts believe up to 288 million people will have the disease by 2040. Although there is no known cause of the disease, researchers believe there may be reliable biomarkers that can predict the disease, or at least identify prognosis. These biomarkers may help optimize treatment and improve outcomes in people affected by macular degeneration.
Stages of Age-Related Macular Degeneration
The early stage of age-related macular degeneration is defined by a “dry” form. This form usually does not cause any symptoms or vision loss. The disease also progresses to an intermediate form and sometimes a later “wet” form. Biofluid biomarkers may be an important way to identify the disease and its potential progression. In turn, regular assessment of these biomarkers may help ultimately reduce the burden of the disease across the population.
Metabolomics to Identify Biomarkers of Macular Degeneration
Metabolomics is a study that involves the profiling of small metabolites or molecules. It is believed that this profiling can identify biofluid biomarkers of age-related macular degeneration in humans. Research studies have previously used metabolomics for Alzheimer’s disease and cancer, in addition to other diseases. Metabolomics often employs mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (NMR). These platforms make metabolomics highly cost-effective.
Metabolomics Finds Potential Macular Degeneration Biomarkers in Urine
While blood samples are typically used in metabolomics, urine samples can also be used to study biofluid biomarkers of disease. Urine collection is non-invasive and easy to perform. A new study compared urine metabolomic signatures in patients with age-related macular degeneration versus healthy participants greater than 50 years.
In the study, 252 patients with age-related macular degeneration and 53 healthy controls from Portugal were enrolled. In a second US cohort, researchers included 147 patients with age-related macular degeneration and 47 healthy participants. Urine samples were collected and analyzed with 1H-NMR spectroscopy using a Bruker Avance III HD 500 MHz system.
In the Portugal group, the NMR analysis of urinary metabolomic profiles found lower levels of formate in participants with late-stage disease versus healthy controls. The researchers were able to distinguish patients with late-stage disease from controls in the US by increased ascorbate levels in addition to two unassigned features.
For early age-related macular degeneration, patients in the Portugal cohort had lower levels of 4- hydroxyphenylacetate (4-HPA), formate, inositol, and sucrose relative to healthy controls. Additionally, US patients with early stage age-related macular degeneration had higher levels of citrate and greater changes in three unassigned metabolites compared with US healthy controls.
Current Insights and Future Directions
1H-NMR urinary analyses suggested that age-related macular degeneration correlates with the exhaustion of selected amino acids and citrate at different stages of age-related macular degeneration. Changes in the urine profiles of patients versus healthy controls may indicate that age-related macular degeneration is associated with increased energy requirements. The researchers noted that additional study should explore and validate these findings in order to identify reliable biomarkers for age-related macular degeneration.
Laíns I, Duarte D, Barros AS, et al. Urine nuclear magnetic resonance (NMR) metabolomics in age-related macular degeneration. J Proteome Res. 2019;18(3):1278-1288.