Alternative models for evaluation of ocular toxicological effects of environmental chemicals and pharmaceuticals: a review.

内容摘要

There are various ethical issues and humane concerns regarding the use of animal models for toxicity testing. Ocular toxicology is a less explored field of toxicology. To address these pertinent issues, this review presents perspectives on alternative models for assessing ocular toxicological effects of environmental chemicals and pharmaceuticals. The literature was reviewed using PubMed, Scopus, and Web of Science databases. Ocular tissue serves as a route of exposure to toxic chemicals and pharmaceuticals. Toxicological studies on the eyes have remained an ignored area of research. Interestingly, the historically prominent Draize test for eye irritation is found numerous references as a method for assessing irritability and corrosivity of pharmaceuticals and chemicals. Ocular tissues, like other tissues, are reported to tend to absorb chemicals and metabolize them. The bovine corneal opacity and permeability (BCOP) test (OECD TG 437) and EpiOcular (OECD TG 492) are known alternative in vitro tests used to measure the irritability or corrosivity potential of surfactants, detergents, acids, isopropanol, and metal oxides. Zebrafish serves as an excellent research model for the study of ocular toxicological effects of environmental toxicants due to its retinal anatomy, which resembles that of humans. Its rapid development and transparency in early life stages facilitate the observation of minute changes. Zebrafish adults when exposed to cypermethrin for 9 days reported apoptosis in retinal cells. Likewise, its embryo (4-5 days post fertilization) upon exposure to triphenyltin showed impaired development of retinal axon. When exposed to environmental toxins such as pharmaceuticals, pesticides, heavy metals, and industrial substances, cells in zebrafish undergo oxidative stress, inflammation, and mitochondrial dysfunction. Besides, reduction in photoreceptors, and damage to retinal ganglion cells (RGCs), and optic nerve have also been reported. These injurious effects result in severe eye conditions, including glaucoma, diabetic retinopathy, and toxic optic neuropathies. Research using zebrafish also enables scientists to effectively assess the therapeutic potential of substances which could mitigate or avert toxin-related injury to the eyes. This review emphasizes the significance of alternative models in ocular toxicology research. It also highlights distinct contribution of alternative models to linking exposure of environmental toxins with ocular diseases. Their application not only increases our understanding of visual health but also opens new avenues for the development of innovative therapies and preventive strategies.