Genomics profile of ocular toxicity in zebrafish exposed to environmental contaminants

Abstract

Environmental contaminants present a significant and growing threat to aquatic ecosystems, with a particularly notable impact on the visual systems of aquatic organisms, including zebrafish. Zebrafish (Danio rerio) are increasingly used in toxicological research because of their genetic and physiological similarities to humans, making them an ideal model for studying the effects of environmental toxins. Among the most frequently observed and studied ocular malformations in zebrafish exposed to toxicants are microphthalmia, cyclopia, and coloboma, all of which involve developmental abnormalities of the eyes. A comprehensive review of over 500 scientific articles was conducted to identify the genes and molecular pathways implicated in these ocular defects. The main focus of this review is to explore how a single ocular malformation can be influenced by multiple genes and how these genes interact within complex molecular networks. Through detailed network analysis of microphthalmia, coloboma and cyclopia, we pinpointed 3 key "hub genes" aldh1a3, vsx2, and stra6 which play central roles in all the three ocular malformations. These hub genes include those that exhibit overexpression, downregulation, as well as those affected by knockout, knockdown, and mutations. Furthermore, an effort was made to connect the gene networks underlying different ocular malformations to identify common genetic factors that may be shared across various conditions. Surprisingly the same hub genes identified are the key players in toxicant induced ocular phenotypes. This approach could help uncover genetic pathways that are critical not only for understanding the specific ocular malformations but also for providing insights into the broader mechanisms through which environmental contaminants disrupt ocular development. This review highlights the interconnected nature of genetic factors influencing eye malformations and emphasizes the need for a more integrated view of how these genes contribute to ocular health in the context of toxicant exposure.

Keywords: Coloboma; Genomics; Microphthalmia; Ocular toxicity; Toxicants; Zebrafish.