Turquoise killifish naturally develop hallmarks of age-related macular degeneration with advancing age

Ageing is a major risk factor for developing vision loss diseases such as age-related macular degeneration (AMD). Unfortunately, we do not have the ability to effectively prevent, slow, or stop onset and progression of AMD long term. These challenges with therapeutic development result from poor understanding of disease mechanism and pathogenesis due to a lack of animal models that manifest the hallmark features of disease. Here, we investigated the rapidly ageing turquoise killifish ( Nothobranchius furzeri ) retina for features of human ageing and AMD. We report that the ageing killifish retina expresses genes associated with human retinal disease in the photoreceptors and retinal pigment epithelium (RPE). Our characterisation of the retina identified that killifish spontaneously develop many hallmark features of AMD and human ageing, including photoreceptor deterioration, lipid deposits, outer retinal inflammation, and ceramide accumulation in the RPE with advancing age. Further, we identify a sex-specific difference in the severity of phenotypes. We propose that the turquoise killifish is a highly suitable model for investigating ageing and AMD-related disease mechanisms across the lifespan.