Pannexin-2 deficient zebrafish develop ocular and visual motor behaviour defects

Pannexin-2 (Panx2), unlike the other pannexin channels Panx1 and Panx3, exhibits a unique intracellular distribution, localizing at ER-mitochondria contact sites. These specialized microdomains are crucial for important cellular functions, including calcium homeostasis, lipid transfer, inflammation, and apoptosis. Despite their presence in neurons and glial cells, the function of Panx2 at ER-mitochondria contact sites in neurotransmission remains unclear. Here, we used TALEN technology to develop a Panx2 knockout ( Panx2 ^−/− ) zebrafish model, to investigate its role in neuronal communication. In 6 days, post fertilization TL ( Panx2 ^+/+ ) larvae, Panx2 expression was observed in the inner and outer plexiform layers of the retina and the arborization fields of the optic tract. Transcriptome profiling of Panx2 ^−/− larvae by RNA-seq analysis revealed down-regulation of vision-related genes, specifically those involved in visual and sensory perception and lens development. Behavioral tests showed that loss of Panx2 leads to altered visual motor response (VMR); Panx2 ^−/− larvae exhibited reduced locomotor activity during light phases and increased activity during dark phases. Additionally, the knockout larvae displayed significantly impaired optomotor response (OMR). When we tested the geometric and refractive properties of adult eyes, optical coherence tomography (OCT) analysis of Panx2 ^−/− fish revealed a longer mean axial length and a negative shift in retinal refractive error (RRE) values, both indicative of myopia. Furthermore, the increased corneal thickness observed in Panx2 ^−/− fish corroborated the molecular and behavioural alterations. Our findings highlight a novel role of Panx2 in retinal development, visual perception, and ocular health.