Zebrafish as an Animal Model for Ocular Toxicity Testing: A Review of Ocular Anatomy and Functional Assays

Abstract

Xenobiotics make their way into organisms from diverse sources including diet, medication, and pollution. Our understanding of ocular toxicities from xenobiotics in humans, livestock, and wildlife is growing thanks to laboratory animal models. Anatomy and physiology are conserved among vertebrate eyes, and studies with common mammalian preclinical species (rodent, dog) can predict human ocular toxicity. However, since the eye is susceptible to toxicities that may not involve a histological correlate, and these species rely heavily on smell and hearing to navigate their world, discovering visual deficits can be challenging with traditional animal models. Alternative models capable of identifying functional impacts on vision and requiring minimal amounts of chemical are valuable assets to toxicology. Human and zebrafish eyes are anatomically and functionally similar, and it has been reported that several common human ocular toxicants cause comparable toxicity in zebrafish. Vision develops rapidly in zebrafish; the tiny larvae rely on visual cues as early as 4 days, and behavioral responses to those cues can be monitored in high-throughput fashion. This article describes the comparative anatomy of the zebrafish eye, the notable differences from the mammalian eye, and presents practical applications of this underutilized model for assessment of ocular toxicity.

Stem cells based in vitro models: trends and prospects in biomaterials cytotoxicity studies

“…Some of materials may produce adverse effects on reproduction (teratogenicity) and may lead to DNA damage and therefore, Caenorhabditis elegans is a suitable model for screening cytotoxicity studies [60]. Additionally, Zebrafish and its embryo has been extensively used for studying effects of materials to the ocular, cardiovascular and neural differentiation [61][62][63][64]. Some of the in vitro models used in cytotoxicity studies of biomaterials are shown in table 1.…”

Zebrafish toxicological screening could aid Leishmaniosis drug discovery

“…Zebrafish embryos develop most of the major organ systems present in mammals, including the cardiovascular, nervous and digestive systems, in in less than a week and most of the safety and efficacy assays can be carried out with zebrafish embryo and larvae with data generated biologically relevant [4]. To endorse the 3Rs principles, the tests chosen for the toxicological screening used zebrafish embryos and larvae up to 120 hpf, classified as in vitro models by international Directives.…”

“…Zebrafish embryos and larvae with up to 120 h of life have been considered unprecedented toxicological models, which exhibit a diverse repertoire of biological processes and possess fully integrated vertebrate organ systems [3]. Thus, zebrafish can bridge the gap between in vitro safety assays and mammals' models in a fast and cost-effective manner and would have a key role in accelerating the process of new chemicals development, improving prediction, prioritizing safe compounds, and decreasing testing time and costs substantially [4][5][6].…”

“…It's also an excellent model organism to study liver damage induced by chemical compounds due to the high degree of genetic conservation for enzymes and pathways necessary in drug metabolism, such as ARH receptors, CYP enzymes or ADH isoenzymes, present and functional since the early stages of development [5,8]. In the same way, cardiovascular physiology is also highly conserved between humans and zebrafish at anatomical, cellular, and membrane-biology levels, thus many human cardiovascular drugs have been shown to have identical effects on larvae zebrafish physiology, and numerous human cardiovascular disorders have been recapitulated in zebrafish genetic model [3,4]. The neural activity can be assessed by embryo neurobehavioral biomarkers, related to the neuromuscular function of the central nervous system that can indicate possible changes in neural development, such as synaptogenesis and glial cell growth [9].…”

Analysis of the Expression of Neurotrophins and Their Receptors in Adult Zebrafish Kidney

“…The most important advantages are the small size (reduction in maintenance costs and spaces to be used), high fecundity, and rapidity of embryonic development [31]. This fascinating model can be utilized in mutagenesis analyses and drug screening tests [32][33][34]. It has become a popular model organism used to conduct experiments related to different research fields, such as embryology, genetics, cancer, cardiovascular, and organ and tissue regeneration [35][36][37][38].…”