Pannexin 1a regulates visual system development and ocular integrity in zebrafish

Pannexin 1a (Panx1a), a large-pore ATP release channel broadly expressed in the vertebrate eye, has an unclear role in ocular development. Using a zebrafish Panx1a knockout, we observed progressive ocular phenotypes, including impaired visuomotor behavior, axial myopia, cataract-like lens abnormalities, lens defects, and retinal thinning. Optokinetic response (OKR) assays revealed markedly reduced responsiveness in Panx1a^-/- larvae, with response rates declining from 91.7% to 50% at 20% contrast and from 100% to 41.7% at 100% contrast, along with prolonged saccade intervals (2-fold at 20% and 4-fold at 100% contrast). High-resolution optical coherence tomography (OCT) in adults showed increased normalized axial length (7-8% across ages) and reduced lens-to-axial length ratios (0.58 vs. 0.63 at 8 months). Histology revealed age-dependent lens epithelial disruption and increased light scatter. Retinal analyses demonstrated thinning of the whole retina (10%) and ganglion cell layer (33%), with occasional vascular tortuosity. Together, these findings identify Panx1a as a key regulator of ocular integrity and refractive development in zebrafish.