Toxicity of a seafood toxin, domoic acid, in the retina via modulation of the NRF2 and NF-κB pathways

Domoic acid (DA), a biotoxin, is produced by several species of marine dinoflagellate and diatom during harmful algal bloom events. DA is a neurotoxin, in humans and non-human primates, oral exposure to DA results in gastrointestinal effects, while DA at higher doses leads to neurological symptoms, seizures and memory deficiency. Exposure of humans to DA occurs mainly through consumption of contaminated seafoods containing an accumulation of the toxin. Previously, it was unclear if DA can have toxic effects on the retina. We assessed the toxicity of DA in human retinal cells (ARPE-19) and in zebrafish embryos. DA significantly lowered ARPE-19 cell viability dose-dependently, and decreased anti-oxidative capacity, increased inflammation, and promoted cell death, possibly through modulating the NRF2 and NF-κB signalling pathways. Zebrafish embryos exposed to DA for four days from one day post fertilization (dpf) had an increase in mortality and a decrease in both hatching and heartbeat rate and exhibited morphological abnormalities. DA treatment also significantly downregulated expression of antioxidant genes and upregulated expression of inflammation mediators, as well as causing photoreceptor death in zebrafish embryos. The results demonstrate that consuming seafood containing DA will have potential toxic effects in human retinas.