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Blue light-triggered optogenetic system for treating uveal melanoma

Oncogene volume 39, pages 2118–2124 (2020)Cite this article

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Abstract

Uveal melanoma is the most common intraocular primary malignancy in adults and has been considered a fatal disease for decades. Optogenetics is an emerging technique that can control the activation of signaling components via irradiation with visible light. The clinical translation of optogenetics has been limited because of the need for surgical implantation of electrodes and relatively shallow tissue penetration. As visible light easily penetrates the eyes, we hypothesized that an optogenetics approach can be an effective treatment of uveal melanoma without surgery. In this study, we evaluated the feasibility of this strategy by using a genetically encoded optogenetic system based on reversible blue light-induced binding pairs between Fas-CIB1-EGFP and CRY2-mCherry-FADD. Subretinal injection of B16 cells was performed to create a uveal melanoma model. Plasmids pairs were co-transfected into B16 cells. We found that blue light irradiation dynamically controlled the translocation of FADD to Fas on the plasma membrane and induced the apoptosis of B16 cells transfected with the optogenetic nanosystem in vitro. Moreover, the blue light-controlled optogenetic nanosystem suppressed the growth of uveal melanoma in vivo by inducing apoptosis. These results suggest that light-controlled optogenetic therapy can be used as a potential novel therapeutic strategy for uveal melanoma.

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Fig. 1: Blue light-activated translocation of FADD to Fas in B16 cells.
Fig. 2: Blue light-induced B16 apoptosis by the optogenetic system in vitro.
Fig. 3: In vivo imaging and quantification of TUNEL-positive cells.
Fig. 4: Blue light-controlled optogenetic nanosystem suppressed the growth of uveal melanoma.

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Acknowledgements

We thank Prof. Colin J. Barnstable for his contribution in revising this manuscript. This work was supported by grants from the National Natural Science Foundation of China (81900894, 81671642, 81870651) and Natural Science Foundation of Tianjin (18JCQNJC11300).

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  1. These authors contributed equally: Mingliang Zhang, Xiao Lin

Authors and Affiliations

  1. Tianjin Key Laboratory of Retinal Functions and Diseases, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, 251 Fukang Road, Tianjin, 300384, China

    Mingliang Zhang, Xiao Lin, Jinping Zhang, Lin Su, Mingming Ma, Vicki L. Ea, Xun Liu, Liming Wang, Xiaorong Li & Xiaomin Zhang

  2. School of Life Sciences, Tianjin University, 92 Weijin Road, Tianjin, 300072, China

    Jin Chang

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Zhang, M., Lin, X., Zhang, J. et al. Blue light-triggered optogenetic system for treating uveal melanoma. Oncogene 39, 2118–2124 (2020). https://doi.org/10.1038/s41388-019-1119-5

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