Acylcarnitine abnormalities implicate mitochondrial dysfunction in wet AMD patients

Research focus

Acylcarnitine Abnormalities Implicate Mitochondrial Dysfunction in Patients With Neovascular Age-Related Macular Degeneration

Liew G, Tse B, Ho I-V, et al. Invest Ophthalmol Vis Sci. 2020;61(8):32.

https://doi.org/10.1167/iovs.61.8.32

A/Prof Gerald Liew, Centre for Vision Research, Department of Ophthalmology (Westmead Hospital), Westmead Institute for Medical Research, University of Sydney, Sydney, Australia was a recipient of a $100,000 MDFA Research Grant in 2015. His research has now been published in the prestigious Investigative Ophthalmology & Visual Science journal. The purpose of the research project was to decipher the metabolomic signature of age-related macular degeneration (AMD), in order, to discover pathogenic pathways.

As the retina is the most metabolically active tissue in the body with a high concentration of mitochondria and lipids, the research team hypothesised that a defect in mitochondrial function may result in pathology such as AMD. One way of detecting mitochondrial dysfunction is through measuring acylcarnitine levels. Acylcarnitines are the catabolic end products of fatty acids and branched-chain amino acids. A/Prof Liew and his team assessed whether acylcarnitine concentrations, a marker of lipid and mitochondrial metabolism, differed between patients with AMD and controls.

A/Prof Liew and his team conducted a cross-sectional case-control study, cases (n = 81) had neovascular AMD and controls (n = 79) had cataract with no other ocular pathology. Plasma blood samples were assessed for acylcarnitine concentrations.

The study showed that, after multivariable adjustment, C2-carnitine (acetylcarnitine) levels were significantly lower in patients with neovascular AMD compared to controls. In addition, C18:2-DC carnitine (a dicarboxylic acylcarnitine with an 18 carbon side chain and 2 double bonds), levels were significantly higher in patients with neovascular AMD compared to controls. Other acylcarnitines examined were not significantly different between cases and controls. These findings suggest mitochondrial dysfunction could be involved in the pathogenesis of neovascular AMD.

Reflecting on the importance of this research A/Prof Liew stated "It is very difficult to study macular degeneration as we can't biopsy the living eye, so we wondered if we could use a new technique to study blood markers in people with macular degeneration. When we got the final results we were thrilled - our results suggested that mitochondria, the power stations of the cells, may not be working properly in macular degeneration. Even better, our findings suggested a way to correct this defect, and potentially help treat macular degeneration. We are now studying this in more detail and trying to develop a potential new treatment. All thanks to the MDFA funding our initial research! "

Apply for the MDFA 2020 Research Grants before 31 January 2021