192. A naturally-derived compound Schisandrin B enhanced light sensation in the pde6c zebrafish model of retinal degeneration.

Zhang L[1], Xiang L[1,2], Liu Y[3], Venkatraman P[1], Chong L[1], Cho J[1], Bonilla S[1], Jin Z[2], Pang CP[4], Ko KM[5], Ma P[3], Zhang M[6], Leung YF[1,7]

[1] Department of Biological Sciences, Purdue University, 915 W. State Street, West Lafayette, IN, 47907, United States of America.
[2] Laboratory for Stem Cell & Retinal Regeneration, Division of Ophthalmic Genetics, The Eye Hospital of Wenzhou Medical University, Wenzhou 325027, China.
[3] Department of Statistics, University of Georgia, 101 Cedar St, Athens, GA 30602, United States of America.
[4] Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, Hong Kong, China.
[5] Division of Life Science, Hong Kong University of Science and Technology, Clear water bay, Hong Kong.
[6] Joint Shantou International Eye Center, Shantou University & the Chinese University of Hong Kong, Shantou, China.
[7] Department of Biochemistry and Molecular Biology, Indiana University School of Medicine Lafayette, 625 Harrison Street, West Lafayette, IN 47907, United States of America.

Retinal degeneration is often progressive. This feature has provided a therapeutic window for intervention that may extend functional vision in patients. Even though this approach is feasible, few promising drug candidates are available. The scarcity of new drugs has motivated research to discover novel compounds through different sources. One such example is Schisandrin B (SchB), an active component isolated from the five-flavor fruit (Fructus Schisandrae) that is postulated in traditional Chinese medicines to exert prophylactic visual benefit. This SchB benefit was investigated in this study in pde6cw59, a zebrafish retinal-degeneration model. In this model, the pde6c gene (phosphodiesterase 6C, cGMP-specific, cone, alpha prime) carried a mutation which caused cone degeneration. This altered the local environment and caused the bystander rods to degenerate too. To test SchB on the pde6cw59 mutants, a treatment concentration was first determined that would not cause morphological defects, and would initiate known physiological response. Then, the mutants were treated with the optimized SchB concentration before the appearance of retinal degeneration at 3 days postfertilization (dpf). The light sensation of animals was evaluated at 6 dpf by the visual motor response (VMR), a visual startle that could be initiated by drastic light onset and offset. The results show that the VMR of pde6cw59 mutants towards light onset was enhanced by the SchB treatment, and that the initial phase of the enhancement was primarily mediated through the mutants’ eyes. Further immunostaining analysis indicates that the treatment specifically reduced the size of the abnormally large rods. These observations implicate an interesting hypothesis: that the morphologically-improved rods drive the observed VMR enhancement. Together, these investigations have identified a possible visual benefit of SchB on retinal degeneration, a benefit that can potentially be further developed to extend functional vision in patients.