Abstract
Okadaic acid (OA) and domoic acid (DA) are biotoxins produced by several species of marine dinoflagellate and diatom, respectively, during harmful algal bloom events. OA is a neurotoxin and phosphatase inhibitor widely known to accumulate in black sponges and is associated with seafood poisoning. Evidence from in vitro and in vivo studies demonstrates that -OA exposure causes neurotoxicity in addition to the diarrheal syndrome. In contrast, DA is a cyclic amino acid, a neurotoxin and a potent agonist of ionotropic glutamate receptors in the central nervous system. In humans and non-human primates' oral exposure to DA elicits gastrointestinal effects, while slightly higher doses cause neurological symptoms, seizures, memory impairment, and limbic system degeneration. Humans can be exposed to OA or DA by consuming contaminated shellfish that have accumulated toxins during algal blooms. It is unclear whether OA or DA exposure affects retinal function, a part of the central nervous system. We evaluated the toxicity of OA or DA in human retinal pigment epithelial cells(ARPE-19) and zebrafish retinas. Cell-based assays determined that both OA and DA significantly decreased cell viability in a dose-dependent manner and increased oxidative stress, inflammation and cell death compared to the untreated control group. In the in vivo study, zebrafish embryos at 24 hours post fertilization (hpf) were treated with/without OA or DA for four days, and endpoint measurements including mortality, malformations, delayed hatching, altered hatching, altered heartbeat and reduced movement were performed. OA or DA exposure increased mortality, decreased hatching and heartbeat rate, and caused morphological abnormalities. OA or DA exposure also markedly decreased the expression of antioxidant genes, significantly
increased inflammation, and evoked a loss of photoreceptors in zebrafish embryos. The data suggest that consuming OA or DA-contaminated seafood can induce retinal toxicity.
| Date of Award | 2021 |
|---|---|
| Original language | English |
| Awarding Institution |
|
| Sponsors | Angolan Government |
| Supervisor | Xinhua Shu (Supervisor) & Patricia Martin (Supervisor) |