The selective serotonin reuptake inhibitor sertraline causes ocular toxicity in larvae of zebrafish (Danio rerio)

Introduction Selective serotonin reuptake inhibitors (SSRIs) are currently the highest prescribed class of antidepressants and are frequently detected in aquatic ecosystems. They act by increasing synaptic concentrations of serotonin, a neurotransmitter which is also involved in neuronal development. A knowledge gap remains regarding the effects of SSRIs on visual function, a process heavily relying on the neuronal system. Methods To close this knowledge gap, zebrafish ( Danio rerio ) embryos were exposed to the SSRI sertraline (SER) at sublethal concentrations of 1, 10, 100 and 1000 µg/L. Effects on the visual system were assessed at multiple levels of biological organisation in larvae exposed for 96 h, and measurements included visual function, retinal structure, and expression of genes involved in visual function and eye development. Results Visual function was affected after exposure to 100 and 1000 µg/L of SER, while retinal structure was significantly affected after exposure to 1000 µg/L of SER. To study the molecular processes behind these effects, gene expression was assessed, pointing out dysregulation of multiple opsin genes, as well as genes involved in retinoic acid metabolism and eye development, namely rho , opn1sw1 , opn1mw1 , rlbp1b , gnat2 , and crx . While expression of these genes was significantly downregulated at 48 hrs post fertilisation (hpf), no significant effects were detected at 96 hpf. Discussion The present study points out the ability of SER to cause adverse effects to visual function, a key process for early life stage fish survival. However, these effects were detected at exposure concentrations exceeding the environmental one, thus not representing an environmental threat.