The Biomarker Breakdown

It’s a classic “chicken and egg” scenario. When retinal diseases like age-related macular degeneration (AMD) strike, early diagnosis and intervention give the best prognosis and visual outcomes. But in reality, retinal disease cannot be diagnosed until structural changes are seen, and some patients only present at ophthalmology clinics when the visual symptoms – and the underlying pathology – are at an advanced stage. Now, a team from Massachusetts Eye and Ear Hospital, Boston, USA, are proposing that metabolomics analysis might hold the key to identifying those at risk during the early stages of disease diagnosis – or even before the disease starts to develop (1).

“Metabolomics has recently been shown to provide biologically informative markers of complex diseases, such as Alzheimer’s, so we decided to research the role of metabolomics in AMD to find biomarkers for diagnosis and prognosis in this disease,” says Deeba Husain, co-senior author on the corresponding paper (1).

In the study, the team took blood plasma samples from 90 patients with AMD (30 each with early, intermediate and late stage disease) and from 120 patients with normal macular health. The samples were analyzed using ultra high-performance liquid chromatography coupled to tandem mass spectrometry. They found that a total of 87 metabolites, mostly from glycerophospholipid metabolism, differed significantly between patients with AMD and the controls. Of these, 48 were significantly different across the different stages of AMD. “We were surprised to find that glycerophospholipid metabolism specifically seems to have a strong association with AMD – this pathway was highly enriched among the significant metabolites (p=4.7 x 10-9),” says Husain, who believes the results could form the basis of the first blood biomarker for early diagnosis and prognosis of AMD.

But their results aren’t just important for diagnosing disease. “The detection of very significant metabolite pathways could lead to finding a new druggable target for treatment,” says Husain, “and that could lay the path for personalized medicine in the management of AMD.”  Next steps for the team include a large multicenter study to validate their findings, as well as a long-term follow-up study to better define the role of glycerophospholipid metabolism in disease progression.