Zebrafish Ocular Toxicity
More than 200 currently used drugs are associated with ophthalmic toxicity due to adverse drug reactions. The toxic effects of drugs on vision are significant, with approximately 6.8% of drugs removed from clinical trials because of visual toxicity. Remarkably, adverse effects associated with drug-induced ocular toxicity are difficult to manage once they occur, and even though gastrointestinal and cardiovascular toxicities are of higher incidence, ocular toxicity has the highest negative influence on drug development. Thus, there is a need for efficient and predictive pre-clinical assays of ocular toxicity that can eliminate drugs that induce visual toxicity in early development phases. However, this process is partly hindered because of a lack of predictive, convenient methods as well as the high expense associated with testing drug candidates in mammals.
Figure 1. Comparison of the human and zebrafish eye.
The vertebrate eye is highly conserved; therefore, zebrafish provide an ideal model for studying ocular toxicity. Besides obvious anatomical similarities, including the cornea, retina, lens, and choroid, as well as innervation and vascularization, the human and zebrafish eye have conserved gene expression, cellular makeup, and tissue architecture. Many studies have shown concordance between results from zebrafish vision assays and human ocular reactions to drugs, including chlorpromazine, quinine, cisplatin, gentamicin, deferoxamine, minoxidil, thioridazine, and vardenafil, among others. By testing drugs with no established human ocular effects as well as the oculartoxic drugs, those authors reported that the zebrafish assays were sensitive 68-83% of the time and specific 75-100% of the time, suggesting utility for detecting oculartoxic chemicals.
Our Zebrafish Ocular Toxicity Assessments
With years of experience and advanced technologies, Creative Biogene has developed several approaches to investigate zebrafish visual function, including optomotor response (OMR) assay, optokinetic response assay, escape response, startle response, and visual motor response assay. Among these, the OMR assay and the visual motor response assay have good throughput properties, and have been used to assess the ocular toxicity of compounds.
- Optokinetic response (OKR)
The OKR is based on the eye movement reflex in response to a moving stimulus to help stabilize the image on the retina to maintain visual acuity and is evidence of a fully functional visual system in zebrafish. The OKR is tracking eye movements, which consists of smooth pursuits and fast resetting saccades in the opposite direction. In the optokinetic assay, dark and light alternating vertical stripes are passed around an immobilized fish, and eye saccades are counted as an indicator of healthy eye response to moving stimuli.
- Optomotor response (OMR)
The OMR tests the visual behavior of zebrafish through their tendency to swim towards moving black and white stripes. In the optomotor assay, zebrafish are free swimming and allowed to respond to temporal or spatial changes in light. As numerous zebrafish with possible visual function defects can be tested at once, this OMR assay can achieve higher-throughput analysis compared with the OKR.
Our Advantages
- Wide ranges of detection technologies
- Easy and flexible workflow
- Produce reliable and quantifiable behavioral data
- Advanced high-content screening equipment
- Excellent predictability
Contact us to learn more about our ocular toxicity assessment services.
References
- Chhetri J, et al. Zebrafish—on the move towards ophthalmological research. Eye, 2014, 28(4): 367-380.
- Cassar S, et al. Use of Zebrafish in Drug Discovery Toxicology. Chemical Research in Toxicology, 2019.
- Sadamoto K, et al. Absence of histopathological changes in the retina of zebrafish treated with sodium iodate. Journal of Veterinary Medical Science, 2018: 17-0613.
- Deeti S, et al. Early safety assessment of human oculotoxic drugs using the zebrafish visualmotor response. Journal of pharmacological and toxicological methods, 2014, 69(1): 1-8.
For research use only. Not intended for any clinical use.
