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Yuk Fai Leung, Liyun Zhang, Leelyn Chong, Jin Cho, Kam Ming Ko; SCHISANDRIN B IMPROVES THE VISUAL MOTOR RESPONSE AND PRESERVES PHOTORECEPTORS IN THE ZEBRAFISH PDE6C CONE DYSTROPHY MUTANT. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1943.
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© ARVO (1962-2015); The Authors (2016-present)
Schisandrin B (Sch B), an active component of Fructus Schisandrae, has been indicated in traditional Chinese medicine (TCM) to offer eye benefits. This study investigated the extent to which Sch B could improve retinal degeneration in the zebrafish pde6c cone dystrophy mutant.
A titration series of Sch B was first conducted to identify a treatment dosage that would activate G6PD, a known marker of Sch B treatment, without affecting the gross morphology. Then, pde6c and wild-type (WT) siblings were treated with the optimized 1.875 µM Sch B or equal amount of DMSO carrier from 3 days post-fertilization (dpf) to 6 dpf. The treatment scheme was chosen because it was theorized that most TCMs play a protective role in diseases and thus, the best chance to determine the protective effect of the treatment would be before any observable photoreceptor degeneration at 4 dpf. The visual performance of the resulting larvae was analyzed by optokinetic response (OKR) and visual-motor response (VMR), a light-induced swimming activity (Zhang et al., Asia-Pac J Ophthalmol 2012; 1:374-383; Emran et al., J Vis Exp. 2008;3(20)). The VMR in this study was optimized to detect light-induced response originated from the eyes, as the VMR was mostly abolished in the enucleated larvae. The photoreceptors in these embryos were also analyzed by immunohistochemistry and qPCR
The pde6c larvae elicited a substantially reduced VMR; thus, their activity profile was very different from the WT siblings. Treating pde6c with 1.875 µM Sch B increased their VMR in response to the light-ON but not the light-OFF stimulus and the OKR. Interestingly, the histological analyses indicated that the rods were preserved in the pde6c mutants and no noticeable difference in the cones. These observations are also supported by a substantial increase in the expression of gnat1 (rod marker) but not gnat2 (cone marker) in the qPCR results.
Sch B might have improved the VMR of pde6c mutants by the preserving their rods. Since one of the best known functions of Sch B is its antioxidant property, oxidative stress is implied to play a role in cell death of the rods in the pde6c mutants. In addition, this study has established the utility of using VMR in zebrafish for identifying drugs that may have eye benefits.
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