Proposing Zebrafish As a Model for Stargardt Disease

Stargardt disease (STGD1) is an inherited juvenile macular degeneration caused by mutations in the ATP-binding cassette subfamily A member 4 gene (ABCA4), a flippase located in the photoreceptor outer segment. ABCA4 mutations cause the buildup of a toxic byproduct in the retina called lipofuscin resulting in the death of photoreceptors by ferroptosis. Mammalian disease models (e.g., mouse Abca4) have been established, but do not replicate all the disease symptoms in human STGD1 patients. It is challenging to model a cone degeneration disease like STGD1 using mice. Here we suggest zebrafish (Danio rerio) as a STGD1 model. This widely used vertebrate model organism is popular in the ocular field due to the early development of a cone-rich retina and the ability to correlate genotypes with relevant phenotypes. Zebrafish have been used to successfully model cone photoreceptor diseases including gene editing and drug-induced models. We propose zebrafish as a suitable diurnal model for STGD1.