Visual and behavioral toxicity of erythritol alone and in combination with high glucose in zebrafish larvae:...

This study investigated erythritol's visual toxicity and its combined effects in a high glucose-induced diabetic retinopathy model using zebrafish larvae (3-6 dpf). Erythritol alone induced abnormal ocular morphology, retinal thinning, and dysregulation of phototransduction, retinol metabolism, and the HPT axis. Crucially, it disrupted the non-image-forming (NIF) pathway, evidenced by the aberrant expression of intrinsically photosensitive retinal ganglion cell (ipRGC) markers (opn4a/b, brn3b). These structural and molecular impairments manifested as significant behavioral deficits, including increased thigmotaxis, reduced locomotion, and impaired color discrimination. Dysregulation of serotonergic genes (htr family and tph2) was associated with the observed behavioral alterations. In the high-glucose model, co-exposure exacerbated structural damage and further disturbed genes involved in lens development and the HPT axis, significantly reducing color preference. Collectively, erythritol induces multifaceted visual impairments and anxiety like behavior through the combined disruption of the NIF-phototransduction-retinol metabolism-HPT axis. These findings highlight the necessity for cautious risk assessment of erythritol use in populations with metabolic diseases.