Estrogen produced in the retina by brain aromatase plays a significant role in zebrafish eye development

Aromatase is a key enzyme in estrogen biosynthesis, expressed in multiple tissues including the brain and retina. In teleost fish, Aromatase B (AroB), encoded by cyp19a1b, is brain-specific and highly expressed during early development, suggesting a role in neurogenesis. Here, we investigated the role of AroB in zebrafish eye development using morpholino (MO)-mediated knockdown. Injection of AroB MO into fertilized eggs reduced eye size (eye-to-body length ratio), decreased optic nerve diameter at 48 h post-fertilization (hpf), and increased apoptosis in the eye at 24 hpf. These defects were rescued by co-injection of AroB mRNA or treatment with 1 μM 17β-estradiol (E2). Functional assays revealed impaired visual background adaptation (VBA) at 5 days post-fertilization (dpf) and defective optomotor response (OMR) at 7 dpf in AroB morphants. Immunostaining with AroB antiserum confirmed a reduction in retinal AroB expression in knockdown larvae. To assess the role of estrogen receptors (ERs), embryos were exposed to selective antagonists. The ERα antagonist MPP had no effect on eye size, optic nerve diameter, or apoptosis. In contrast, the ERβ antagonist CYC reduced eye size and optic nerve diameter, while increasing apoptosis. The non-selective ER antagonist ICI also reduced eye size and elevated apoptosis, though it did not alter optic nerve diameter. Behaviorally, VBA was reduced by ICI and CYC, but not MPP; OMR was diminished by ICI and MPP, but unaffected by CYC. Together, these findings demonstrate that estrogen produced in the retina by AroB plays a critical role in zebrafish eye development, with its functions differentially mediated by distinct ER subtypes.