Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo 650-0047, Japan; Kobe City Eye Hospital, Kobe, Hyogo 650-0047, Japan; Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Human Informatics and Interaction Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba 305-8568, Japan.
Stem Cell Reports. 2024 Nov 12;19(11):1524-1533. doi: 10.1016/j.stemcr.2024.09.002. Epub 2024 Oct 3.
Macular hole (MH) is a retinal break involving the fovea that causes impaired vision. Although advances in vitreoretinal surgical techniques achieve >90% MH closure rate, refractory cases still exist. For such cases, autologous retinal transplantation is an optional therapy showing good anatomic success, but visual improvement is limited and peripheral visual field defects are inevitable after graft harvesting. Here, using a non-human primate model, we evaluated whether human embryonic stem cell-derived retinal organoid (RO) sheet transplantation can be an effective option for treating MH. After transplantation, MH was successfully closed by continuous filling of the MH space with the RO sheet, resulting in improved visual function, although no host-graft synaptic connections were confirmed. Mild xeno-transplantation rejection was controlled by additional focal steroid injections and rod/cone photoreceptors developed in the graft. Overall, our findings suggest pluripotent stem cell-derived RO sheet transplantation as a practical option for refractory MH treatment.
黄斑裂孔 (MH) 是一种累及黄斑的视网膜裂孔，可导致视力受损。尽管玻璃体视网膜手术技术的进步实现了超过 90%的 MH 闭合率，但仍存在难治性病例。对于此类病例，自体视网膜移植是一种可选的治疗方法，具有良好的解剖学成功，但视觉改善有限，并且在进行移植物采集后，周边视野缺损是不可避免的。在这里，我们使用非人类灵长类动物模型评估了人胚胎干细胞源性视网膜类器官 (RO) 片移植是否可作为治疗 MH 的有效选择。移植后，RO 片连续填充 MH 空间，成功闭合 MH，导致视觉功能改善，尽管未确认宿主-移植物突触连接。通过额外的局部类固醇注射和移植物中发育的视杆/视锥感光细胞控制轻微的异种移植排斥反应。总的来说，我们的发现表明多能干细胞源性 RO 片移植是治疗难治性 MH 的一种实用选择。
