Effect of permethrin insecticide on TRβ-mediated cone photoreceptor differentiation and spectral sensitivity in zebrafish larvae (Danio rerio)

Permethrin (PM), a pyrethroid insecticide, is used extensively in both domestic and agricultural settings. Recent data suggest that PM exposure poses substantial physiological hazards, particularly to eyes. However, the mechanisms underlying retinal dysfunction following PM exposure have not been explored comprehensively. In this study, both thyroid hormone receptor β (TRβ)- and SWS1-labeled transgenic zebrafish (cone model) as well as TRβ mutant (TRβ^-/-) zebrafish were exposed to PM in the initial phases of retinogenesis, to elucidate the mechanisms of PM retinal cone toxicity. PM exposure suppressed phototactic behavior and the locomotor trajectory in different wavelengths of light signaling in larvae. Compared with low concentration (0.9 μg/L), medium and high concentration PM (10.2-99.25 μg/L) exposure induced structural damage and mosaic patterning disorder more easily, reduced optical transduction in cones and red-UV cone regularity by interfering with normal cone cell differentiation. Furthermore, in TRβ^-/-, only the differentiation process of red cone was inhibited, and PM exposure no longer induces red cone differentiation, whereas UV cone differentiation was still induced under PM. The data indicated that PM exposure can interfere with cone cell development and differentiation to disturb photosensitivity function. Moreover, PM exposure specialized and promoted transformation of retinal progenitor cells into red cones through the TRβ signaling pathway in larval retina. Given the conserved developmental patterns between zebrafish and human cones, this study highlights that environmentally relevant PM concentrations might pose significant risks to both aquatic organisms and humans via impairing TRβ signaling at the single-cell level, warranting further investigation into their chemical hazards.