College of Veterinary Medicine, Department of Small Animal Clinical Sciences, Michigan State University.
Lineage Cell Therapeutics, Inc.
J Vis Exp. 2021 Aug 5(174). doi: 10.3791/61683.
Retinal degenerative (RD) conditions associated with photoreceptor loss such as age-related macular degeneration (AMD), retinitis pigmentosa (RP) and Leber Congenital Amaurosis (LCA) cause progressive and debilitating vision loss. There is an unmet need for therapies that can restore vision once photoreceptors have been lost. Transplantation of human pluripotent stem cell (hPSC)-derived retinal tissue (organoids) into the subretinal space of an eye with advanced RD brings retinal tissue sheets with thousands of healthy mutation-free photoreceptors and has a potential to treat most/all blinding diseases associated with photoreceptor degeneration with one approved protocol. Transplantation of fetal retinal tissue into the subretinal space of animal models and people with advanced RD has been developed successfully but cannot be used as a routine therapy due to ethical concerns and limited tissue supply. Large eye inherited retinal degeneration (IRD) animal models are valuable for developing vision restoration therapies utilizing advanced surgical approaches to transplant retinal cells/tissue into the subretinal space. The similarities in globe size, and photoreceptor distribution (e.g., presence of macula-like region area centralis) and availability of IRD models closely recapitulating human IRD would facilitate rapid translation of a promising therapy to the clinic. Presented here is a surgical technique of transplanting hPSC-derived retinal tissue into the subretinal space of a large animal model allowing assessment of this promising approach in animal models.
与光感受器损失相关的视网膜退行性（RD）疾病，如年龄相关性黄斑变性（AMD）、色素性视网膜炎（RP）和莱伯先天性黑蒙（LCA），会导致进行性和使人衰弱的视力丧失。人们迫切需要能够在光感受器丧失后恢复视力的治疗方法。将人多能干细胞（hPSC）衍生的视网膜组织（类器官）移植到晚期 RD 眼中的视网膜下空间，可以带来带有数千个健康、无突变的光感受器的视网膜组织片，有可能用一种经过批准的方案治疗大多数/所有与光感受器退化相关的致盲疾病。将胎儿视网膜组织移植到晚期 RD 动物模型和人类的视网膜下空间已成功开发，但由于伦理问题和组织供应有限，不能作为常规治疗方法使用。大型遗传性视网膜疾病（IRD）动物模型对于开发利用先进的手术方法将视网膜细胞/组织移植到视网膜下空间的视力恢复疗法非常有价值。这些模型在眼球大小、光感受器分布（例如，是否存在类似黄斑的中央凹区域）方面的相似性，以及与人类 IRD 非常相似的 IRD 模型的可用性，将有助于将有前途的治疗方法快速转化为临床应用。本文介绍了一种将 hPSC 衍生的视网膜组织移植到大型动物模型视网膜下空间的手术技术，可用于在动物模型中评估这种有前途的方法。
