Development of the zebrafish foveal analogue: a quantitative atlas of high-acuity zone growth and retinal regionalisation

The vertebrate retina contains specialised regions for high-acuity vision, exemplified by the human fovea and its zebrafish analogue, the high acuity zone (HAZ). Despite the widespread use of zebrafish to model retinal disease, a stage-resolved quantitative reference describing normal eye, photoreceptor layer (PRL) and lens growth has been lacking. Here we apply contrast-enhanced micro-computed tomography to construct the first three-dimensional micro-CT normative atlas of wild-type zebrafish eye development across five larval stages (3, 5, 7, 10 and 18 dpf), mapping circumferential PRL thickness, eye and lens morphology, and compartment growth rates. Regional PRL thickening within the temporo-ventral region of the expected HAZ emerged by 5 dpf and was sustained by a localised redistribution of growth, persisting and extending towards the optic nerve through 18 dpf. The PRL, lens and eye grew through four phases, alternating between disproportionate PRL expansion and coordinated growth, while the eye remodelled from a nasal-dominant to a temporo-ventral-dominant form. This regional specialization was protracted relative to gross ocular growth and could proceed independently of it, paralleling the extended postnatal maturation of the human fovea. This atlas provides a quantitative baseline for distinguishing disease-induced changes from normal variation, supporting zebrafish models of foveal hypoplasia and related disorders.