Restoration of visual function in advanced disease after transplantation of purified human pluripotent stem cell-derived cone photoreceptors.
Restoration of visual function in advanced disease after transplantation of purified human pluripotent stem cell-derived cone photoreceptors.
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DOI：
10.1016/j.celrep.2021.109022
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发表时间：
2021-04-20
期刊：
影响因子：
8.8
通讯作者：
Ali RR
中科院分区：
文献类型：
--
作者：
Ribeiro J;Procyk CA;West EL;O'Hara-Wright M;Martins MF;Khorasani MM;Hare A;Basche M;Fernando M;Goh D;Jumbo N;Rizzi M;Powell K;Tariq M;Michaelides M;Bainbridge JWB;Smith AJ;Pearson RA;Gonzalez-Cordero A;Ali RR
老年性黄斑变性和其他黄斑疾病导致光感锥光感受器的丧失，造成不可逆的视力损害。光感受器替代可以通过移植健康细胞来恢复视力，这些细胞必须与受体视网膜形成新的突触连接。尽管最近取得了一些进展，但缺乏令人信服的证据表明，移植的人类视锥光感受器在晚期视网膜变性中具有功能连接。在这里，我们展示了将纯化的人类多能干细胞衍生的视锥细胞移植到晚期变性小鼠模型后视觉功能的恢复。移植的人类视锥细胞精心制作新生的外节，并与受体小鼠双极细胞（bc）形成假定的突触，后者本身经历了重大的重塑。电生理和行为评估显示，在接受治疗的动物中，令人惊讶的复杂的光诱发视网膜神经节细胞反应和改善的光诱发行为得到了恢复。严格的控制排除了其他解释，包括物质转移和神经保护。这些数据为光感受器替代疗法和挽救视锥介导视力的潜力提供了重要的验证。通过纯化的人视锥细胞移植恢复视锥细胞介导的功能在晚期退行性变中复杂视网膜反应和行为的恢复人-鼠推定突触连接的形成相关控制排除物质转移和营养支持视锥光感受器死亡和相关的中枢视力丧失在许多视网膜营养不良症中很常见。Ribeiro等人表明，将纯化的人类多能干细胞衍生的视锥细胞移植到终末期疾病的小鼠模型中，可以与底层视网膜形成功能性连接，并恢复视锥细胞介导的视觉功能。
Age-related macular degeneration and other macular diseases result in the loss of light-sensing cone photoreceptors, causing irreversible sight impairment. Photoreceptor replacement may restore vision by transplanting healthy cells, which must form new synaptic connections with the recipient retina. Despite recent advances, convincing evidence of functional connectivity arising from transplanted human cone photoreceptors in advanced retinal degeneration is lacking. Here, we show restoration of visual function after transplantation of purified human pluripotent stem cell-derived cones into a mouse model of advanced degeneration. Transplanted human cones elaborate nascent outer segments and make putative synapses with recipient murine bipolar cells (BCs), which themselves undergo significant remodeling. Electrophysiological and behavioral assessments demonstrate restoration of surprisingly complex light-evoked retinal ganglion cell responses and improved light-evoked behaviors in treated animals. Stringent controls exclude alternative explanations, including material transfer and neuroprotection. These data provide crucial validation for photoreceptor replacement therapy and for the potential to rescue cone-mediated vision. Rescue of cone-mediated function by transplantation of purified human cones Restoration of complex retinal responses and behavior in advanced degeneration Formation of human-murine putative synaptic connections Relevant controls exclude material transfer and trophic support Cone photoreceptor death and associated central vision loss are common to many retinal dystrophies. Ribeiro et al. show that transplantation of purified human pluripotent stem cell-derived cones into a mouse model of end-stage disease allows the formation of functional connections with the underlying retina and restores cone-mediated visual function.
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影响因子：
5.9
作者：
Assawachananont, Juthaporn;Mandai, Michiko;Okamoto, Satoshi;Yamada, Chikako;Eiraku, Mototsugu;Yonemura, Shigenobu;Sasai, Yoshiki;Takahashi, Masayo
通讯作者：
Takahashi, Masayo
DOI：
10.1073/pnas.250478897
发表时间：
2000-12-05
影响因子：
11.1
作者：
Calvert, PD;Krasnoperova, NV;Lem, J
通讯作者：
Lem, J
影响因子：
5.9
作者：
Iraha S;Tu HY;Yamasaki S;Kagawa T;Goto M;Takahashi R;Watanabe T;Sugita S;Yonemura S;Sunagawa GA;Matsuyama T;Fujii M;Kuwahara A;Kishino A;Koide N;Eiraku M;Tanihara H;Takahashi M;Mandai M
通讯作者：
Mandai M
影响因子：
5.9
作者：
Gonzalez-Cordero A;Kruczek K;Naeem A;Fernando M;Kloc M;Ribeiro J;Goh D;Duran Y;Blackford SJI;Abelleira-Hervas L;Sampson RD;Shum IO;Branch MJ;Gardner PJ;Sowden JC;Bainbridge JWB;Smith AJ;West EL;Pearson RA;Ali RR
通讯作者：
Ali RR
影响因子：
4.6
作者：
Barnea-Cramer AO;Wang W;Lu SJ;Singh MS;Luo C;Huo H;McClements ME;Barnard AR;MacLaren RE;Lanza R
通讯作者：
Lanza R