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.

葡萄膜黑色素瘤是成人最常见的眼内原发性恶性肿瘤，几十年来一直被认为是一种致命疾病。光遗传学是一种新兴技术，可以通过可见光照射来控制信号成分的激活。由于需要手术植入电极和相对较浅的组织穿透，光遗传学的临床转化受到限制。由于可见光很容易穿透眼睛，我们假设光遗传学方法可以有效治疗葡萄膜黑色素瘤而无需手术。在这项研究中，我们通过使用基于 Fas-CIB1-EGFP 和 CRY2-mCherry-FADD 之间的可逆蓝光诱导的结合对的基因编码光遗传学系统来评估该策略的可行性。进行 B16 细胞的视网膜下注射以创建葡萄膜黑色素瘤模型。将质粒对共转染到 B16 细胞中。我们发现蓝光照射动态控制了质膜上FADD向Fas的易位，并在体外诱导了用光遗传学纳米系统转染的B16细胞的凋亡。此外，蓝光控制的光遗传学纳米系统通过诱导细胞凋亡来抑制体内葡萄膜黑色素瘤的生长。这些结果表明，光控光遗传学疗法可用作葡萄膜黑色素瘤的潜在新治疗策略。我们发现蓝光照射动态控制了质膜上FADD向Fas的易位，并在体外诱导了用光遗传学纳米系统转染的B16细胞的凋亡。此外，蓝光控制的光遗传学纳米系统通过诱导细胞凋亡来抑制体内葡萄膜黑色素瘤的生长。这些结果表明，光控光遗传学疗法可用作葡萄膜黑色素瘤的潜在新治疗策略。我们发现蓝光照射动态控制了质膜上FADD向Fas的易位，并在体外诱导了用光遗传学纳米系统转染的B16细胞的凋亡。此外，蓝光控制的光遗传学纳米系统通过诱导细胞凋亡来抑制体内葡萄膜黑色素瘤的生长。这些结果表明，光控光遗传学疗法可用作葡萄膜黑色素瘤的潜在新治疗策略。