TY - JOUR
T1 - A naturally-derived compound schisandrin B enhanced light sensation in the pde6c zebrafish model of retinal degeneration
AU - Zhang, Liyun
AU - Xiang, Lue
AU - Liu, Yiwen
AU - Venkatraman, Prahatha
AU - Chong, Leelyn
AU - Cho, Jin
AU - Bonilla, Sylvia
AU - Jin, Zi Bing
AU - Pang, Chi Pui
AU - Ko, Kam Ming
AU - Ma, Ping
AU - Zhang, Mingzhi
AU - Leung, Yuk Fai
N1 - Funding Information:
Liyun Zhang was partially supported by a Charles Kelman M.D. Postdoctoral Fellowship from the International Retinal Research Foundation. Lue Xiang and Zi-Bing Jin were partially supported the National Key Basic Research Program (Grant No. 2013CB967502), Zhejiang Provincial Natural Science Foundation of China under Grant No. LR13H120001, and the National Natural Science Foundation of China (Grant No. 81522014, 81371059). Prahatha Venkatraman was partially supported by a Faculty for the Future Fellowship from the Schlumberger Foundation. Yiwen Liu and Ping Ma were partially supported by the National Science Foundation (Grant No. DMS-1440037, 1440038, 1438957). Yiwen Liu was also partially supported by the National Institutes of Health (Grant No. 5R01GM113242-02). Chi Pui Pang was partially supported by a Direct grant (Grant No. 2041771) from the Medical Panel, The Chinese University of Hong Kong, and a General Research Fund (Grant No. 2140694) from the Research Grants Council of Hong Kong. Mingzhi Zhang was partially supported by the National Scientific Foundation of China (Grant No. 81486126), the Provincial Natural Scientific Foundation of China (Grant No. 8151503102000019). The authors thank David Prober and Jason Rihel for sharing their experience on using the Zebrabox machine; Skye Brown for her technical assistance; Susan Brockerhoff for sharing her experience on using the pde6c mutant; James Fadool for the 1D1 antibody; Laszlo Csonka for his help on the G6PDH assay; Patrice Baumhardt for her help on spectrometer measurement; Swathi Devireddy for her demonstration of 3D ImageJ Suite; Larry Baum for his proofreading of the final manuscript; and John Dowling, Donna Fekete, Wei Li, William Pak, Donald Ready, Woody Walls and members of the Leung lab for helpful discussions. Liyun Zhang was partially supported by a Charles Kelman M.D. Postdoctoral Fellowship from the International Retinal Research Foundation. Lue Xiang and Zi-Bing Jin were partially supported the National Key Basic Research Program (Grant No. 2013CB967502), Zhejiang Provincial Natural Science Foundation of China under Grant No.LR13H120001, and the National Natural Science Foundation of China (Grant No. 81522014, 81371059). Prahatha Venkatraman was partially supported by a Faculty for the Future Fellowship from the Schlumberger Foundation. Yiwen Liu and Ping Ma were partially supported by the National Science Foundation (Grant No. DMS- 1440037, 1440038, 1438957). Yiwen Liu was also partially supported by the National Institutes of Health (Grant No. 5R01GM113242-02). Chi Pui Pang was partially supported by a Direct grant (Grant No. 2041771) from the Medical Panel, The Chinese University of Hong Kong, and a General Research Fund (Grant No. 2140694) from the Research Grants Council of Hong Kong. Mingzhi Zhang was partially supported by the National Scientific Foundation of China (Grant No. 81486126), the Provincial Natural Scientific Foundation of China (Grant No. 8151503102000019).
Publisher Copyright:
© 2016 Zhanget al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2016/3
Y1 - 2016/3
N2 - 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 retinaldegeneration 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.
AB - 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 retinaldegeneration 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.
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U2 - 10.1371/journal.pone.0149663
DO - 10.1371/journal.pone.0149663
M3 - Article
C2 - 26930483
AN - SCOPUS:84960984271
VL - 11
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 3
M1 - e0149663
ER -