Nouri, N., Gussler, B.H., Stockwell, A., Truong, T., Kang, G.J., Browder, K.C., Malato, Y., Sene, A., Van Everen, S., Wykoff, C.C., Brown, D., Fu, A., Palmer, J.D., Lima de Carvalho, J.R., Ullah, E., Al Rawi, R., Chew, E.Y., Zein, W.M., Guan, B., McCarthy, M.I., Hofmann, J.W., Chaney, S.Y., Jasper, H., Yaspan, B.L. (2024). SLC16A8 is a causal contributor to age-related macular degeneration risk.  NPJ Genom Med 9(1): 50.

FBrf0260860

Research paper

Age-related macular degeneration (AMD), a complex neurodegenerative disease, is a leading cause of visual impairment worldwide with a strong genetic component. Genetic studies have identified several loci, but few causal genes with functional characterization. Here we highlight multiple lines of evidence which show a causal role in AMD for SLC16A8, which encodes MCT3, a retinal pigment epithelium (RPE) specific lactate transporter. First, in an unbiased, genome-wide analysis of rare coding variants we show multiple SLC16A8 rare variants are associated with AMD risk, corroborating previous borderline significant reports from AMD rare variant studies. Second, we report a novel SLC16A8 mutation in a three-generation family with early onset macular degeneration. Finally, mis-expression in multiple model organisms shows functional and anatomic retinal consequences. This study highlights the important role for SLC16A8 and lactate regulation towards outer retina/RPE health and highlights a potential new therapeutic opportunity for the treatment of AMD.

PMC11519927 (PMC) (EuropePMC)