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.