Rapid drug discovery for retinal degeneration
Zebrafish is a highly visual animal, and the change of its visual behaviors has been used for identifying mutants for retinal degeneration. For example, an optokinetic response (OKR) can be used to identify a retinal degeneration mutant that is morphologically normal.
OKR of a normal sibling (bottom) and a retinal degeneration mutant (top) embryo. These embryos are put inside a rotating drum with black and white stripes (a reflection can be seen in the air bubble on the left). While both embryos look normal, only the bottom one can track the rotating stripes and move its eyes accordingly.
Histological analysis of the retinas of these embryos indicates that the photoreceptors are degenerating in the mutant and are not in the normal sibling, thus explaining why the mutant does not respond in the OKR test. Courtesy of Liyun Zhang, a postdoctoral fellow in the laboratory.
Since the little zebrafish embryos can absorb chemicals through their skin, thus we can put drugs in the water. Through the improvements of the visual behaviors and associated histology, we can efficiently evaluate the potential therapeutic value of the drugs. We are in the process of establishing another visual activity assay that can conduct drug screening on 96-well plates; this will expedite drug development and is a focus of the Purdue Drug Discovery Initiative. There is no other vertebrate model that can achieve such high-throughput model of investigation, and our group is very excited by this unique opportunity to help eye disease patients.
We are particularly interested in screening traditional Chinese medicines (TCMs) for better vision. To this end, we are collaborating with a number of prominent centers in Hong Kong and China and have acquired pure compounds, extracts and herbal formulas that are good for vision and/or have been used to treat Chinese retinal degeneration patients successfully. Together with our unique approaches for studying “Disease-causing gene network for retinal degeneration”, we can effectively deduce the molecular pathways through which the drug candidates exert their therapeutic effects.