Polystyrene nanoplastics chronic exposure cause zebrafish visual neurobehavior toxicity through TGFβ-crystallin axis

The ubiquitous presence of micro-and nanoplastics (MNPs) in the environment and everyday products has attracted global attention for their hazardous risks. However, the effects and underling mechanisms of MNPs chronic exposure on behavioral/visual changes of the adult and offspring remain unclear. The present study investigated the impact of polystyrene (PS) nanoplastics of 80, 200 and 500 nm diameters on zebrafish visual behaviors at an environmentally relevant concentration of 0.1 mg/L. Exposure to PS resulted in zebrafish hyperactivity, enhanced aggression, compacted shoaling and less sociability, and especially suppressed the adult optokinetic response (OKR) and offspring larval phototactic behavior, with the 500 nm PS being the most detrimental. Histopathological analysis showed 500 nm PS caused significant structural damage to the retina's pigment epithelium (RPE), photoreceptor cells (PRC), and crystalline lens. Fluorescence observation found PS accumulation in retinal layers correlated with reduced oligodendrocyte transcription factor 2 (Olig2) in optic nerve. Further transcriptomic analysis of the adult eye tissue revealed that 500 nm PS affected the transforming growth factor β (TGFβ) and phototransduction signaling pathways, dysregulated visual perception and lens development, potentially leading to dysopia in zebrafish. Specifically, TGFβ and its regulated-extracellular matrix/inflammatory factors and crystallin genes were increased, but the visual perception genes were decreased, suggesting the TGFβ-crystallin axis disorders contribute to the eye dysfunction induced by PS exposure. Collectively, our results provide new evidence revealing the molecular mechanisms of PS-induced visual toxicity and neurobehavioral changes highlighting that MNPs may pose a risk to vision health.