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Heather Prior, Dylan Van Gaalen; Lanosterol treatment of induced cataracts in adult zebrafish shows reduction of cataract severity. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1116.
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This study was designed to evaluate the effectiveness of lanosterol as a treatment for induced cataracts in zebrafish. As an important model organism, zebrafish offer opportunities to investigate basic as well as medical research questions in the field of cataractogenesis. Recent studies using rabbit, dog and human lenses have shown promising results for the treatment of cataracts using lanosterol. We have previously developed a method for the induction of cataracts in adult zebrafish which was used to produce cataracts in our study animals. We used extracted zebrafish lenses to demonstrate the effects of lanosterol treatment on lens clarity. The effects of lanosterol treatment on living fish with induced cataracts was also assessed using the optokinetic response (OKR) to quantify visual recovery.
Adult zebrafish were subjected to intraocular injection of 3% hydrogen peroxide to induce cataracts. At 24 hours post-injection, fish were anesthetized for observation of cataract severity, and lenses were extracted for in vitro treatment with lanosterol. As controls, lenses without cataracts were also extracted and cataract lenses without lanosterol treatment were observed. Lens clarity was assessed by photography of the lens placed over a grid. Lanosterol treatment of living fish with induced cataracts was carried out by intraocular injection of lanosterol, by topical application of lanosterol, or by a combination of application methods. For OKR analysis, fish were immobilized and placed within a rotating drum of black and white stripes, and eye movements were recorded with a video camera. Fish were analyzed both prior to and after cataract induction, with and without lanosterol treatment, at various time points.
Using a scoring scale of 1 to 4, observations showed consistent reduction of cataract severity after lanosterol treatment in extracted lenses as compared to controls as soon as 24 to 48 hours after treatment. OKR analysis of fish with cataracts varied depending on the treatment frequency and modality (injection or topical) .
These results support the findings in other species that lanosterol may be an effective restorative agent for lens clarity in individuals with cataracts. In addition, it demonstrates that our method of inducing cataracts in zebrafish is a tractable experimental system.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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