Zebrafish (Danio rerio) Is an Economical and Efficient Animal Model for Screening Potential Anti-cataract Compounds

PURPOSE: To develop a zebrafish cataract model for screening potential anti-cataract compounds. METHODS: Living zebrafish were anesthetized and exposed to ultraviolet-C (UV-C) irradiation at a dosage of 3250 mJ/cm(2)/d until they developed severe cataracts. These cataracts were graded based on photographs analyzed with ImageQuant TL version 7.0. Fish with severe cataracts were used to evaluate a range of compounds for cataract treatment, including the previously demonstrated hit compound lanosterol. For the initial evaluation, fish were divided into four groups: no treatment, balanced salt solution, β-cyclodextrin (β-CD), and lanosterol dissolved in β-CD. The treatments were performed for 10 days, and the clarity of lenses was evaluated. To assess the persistence of treatment, fish were treated with β-CD and lanosterol dissolved in β-CD for seven consecutive days followed by monitoring for three days without treatment. RESULTS: The average time for zebrafish to develop severe cataracts using the present UV-C irradiation protocol was 7.8 days (range 4–15 days). Both study designs required only another 10 days to determine the effect of hit compounds. The total experimental period could be completed within one month, and the entire experiment was economical. CONCLUSIONS: We could assay a large number of hit compounds at a reasonable cost and within a short time using this newly developed zebrafish cataract model. These assays may allow development of an efficient platform for screening potential anti-cataract compounds. TRANSLATIONAL RELEVANCE: The results may facilitate the development of ani-cataract medication for humans after further experiments and investigations.