Stem cell-based transplantation therapies offer hope for currently untreatable retinal degenerations; however, preclinical progress has been largely confined to rodent models. Here, we describe an experimental platform for accelerating photoreceptor replacement therapy in the nonhuman primate, which has a visual system much more similar to the human. We deployed fluorescence adaptive optics scanning light ophthalmoscopy (FAOSLO) to noninvasively track transplanted photoreceptor precursors over time at cellular resolution in the living macaque. Fluorescently labeled photoreceptors generated from a CRX^+/tdTomato human embryonic stem cell (hESC) reporter line were delivered subretinally to macaques with normal retinas and following selective ablation of host photoreceptors using an ultrafast laser. The fluorescent reporter together with FAOSLO allowed transplanted photoreceptor precursor survival, migration, and neurite formation to be monitored over time in vivo. Histological examination suggested migration of photoreceptor precursors to the outer plexiform layer and potential synapse formation in ablated areas in the macaque eye.

基于干细胞的移植疗法为目前无法治疗的视网膜变性带来了希望；然而，临床前进展主要局限于啮齿动物模型。在这里，我们描述了一个加速非人类灵长类动物光感受器替代疗法的实验平台，该动物的视觉系统与人类更加相似。我们部署了荧光自适应光学扫描光检眼镜 (FAOSLO)，以细胞分辨率无创地跟踪活体猕猴体内移植的光感受器前体随时间的变化。将由 CRX ^+/tdTomato人类胚胎干细胞 (hESC) 报告系产生的荧光标记光感受器递送到视网膜下至具有正常视网膜的猕猴，然后使用超快激光选择性消融宿主光感受器。荧光报告基因与FAOSLO一起可以在体内监测移植的光感受器前体的存活、迁移和神经突形成。组织学检查表明光感受器前体迁移到外丛状层，并且在猕猴眼的消融区域可能形成突触。