Metabolomics may enable early diagnosis, treatment in macular degeneration
Investigators reported that patients with age-related macular degeneration have a distinct plasma metabolomic profile compared with controls, according to research presented at the American Society of Retina Specialists annual meeting.
“Age-related macular degeneration is a leading cause of blindness in the world, yet there are several very important unmet needs for this multifactorial disease, which includes lack of complete understanding of disease pathogenesis, lack of accessible and reliable biomarkers for diagnosis and prognosis, and lack of treatments for all forms of dry AMD,” Deeba Husain, MD, of Harvard Medical School and Massachusetts Eye and Ear, said in the presentation. “We believe that metabolomics can be an appropriate approach to address these unmet needs.”
Husain and colleagues compared the plasma metabolomic profiles of AMD patients and controls in two distinct cohorts in a prospective, cross-sectional study at two sites (Boston and Coimbra, Portugal).
The researchers collected patient’s detailed history, performed eye exams, color fundus photographs (AMD graded using AREDS classification) and SD-OCT, and analyzed fasting blood samples using ultra-performance liquid chromatography and high-resolution mass spectrometry. They conducted multivariate analysis to evaluate clustering between AMD and controls as well as a meta-analysis. Using the tool Metaboanalyst 4.0, they assessed biological relevance of significant metabolites.
Overall, 149 patients with AMD and 47 controls from the U.S. and 242 patients with AMD and 53 controls from Portugal were included in the study.
Analyses were performed on 544 metabolites, according to the presentation. Meta-analysis revealed 69 significantly different metabolites (P < .05) in patients with AMD and controls, 28 of whom achieved a statistically significant false discovery rate. Husain and colleagues found that most of the significant metabolites were lipids (35.7%), followed by amino acids (28.6%), nucelotides (21.4%), carbohydrates (7.1%), cofactors and vitamins (3.6%) and peptides (3.6%).
After conducting pathway analysis of the 28 significant metabolites, the researchers reported a significant enrichment for purine (P = 7.2 x 10-4), sphingolipid (P = .001), glycerophospholipid (P = .0037), and nitrogen metabolites (P = .0404).
“This validates our initial work which shows that plasma metabolomics enable distinction of AMD patients and controls, most of our metabolites are lipids and amino acids, and metabolomics offers a potential novel tool for early diagnosis and treatment and may point to new druggable targets for the treatment of macular degeneration,” Husain concluded.
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Husain D, et al. Role of Metabolomics in Age-Related Macular Degeneration. Presented at: American Society of Retina Specialists annual meeting; July 24-26, 2020 (virtual meeting).
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