PDF(Pubmed)
Abstract：
End-stage age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are two major retinal degenerative (RD) conditions that result in irreversible vision loss. Permanent eye damage can also occur in battlefields or due to accidents. This suggests there is an unmet need for developing effective strategies for treating permanent retinal damages. In previous studies, co-grafted sheets of fetal retina with its retinal pigment epithelium (RPE) have demonstrated vision improvement in rat retinal disease models and in patients, but this has not yet been attempted with stem-cell derived tissue. Here we demonstrate a cellular therapy for irreversible retinal eye injuries using a \"total retina patch\" consisting of retinal photoreceptor progenitor sheets and healthy RPE cells on an artificial Bruch\'s membrane (BM). For this, retina organoids (ROs) (cultured in suspension) and polarized RPE sheets (cultured on an ultrathin parylene substrate) were made into a co-graft using bio-adhesives [gelatin, growth factor-reduced matrigel, and medium viscosity (MVG) alginate]. In vivo transplantation experiments were conducted in immunodeficient Royal College of Surgeons (RCS) rats at advanced stages of retinal degeneration. Structural reconstruction of the severely damaged retina was observed based on histological assessments and optical coherence tomography (OCT) imaging. Visual functional assessments were conducted by optokinetic behavioral testing and superior colliculus electrophysiology. Long-term survival of the co-graft in the rat subretinal space and improvement in visual function were observed. Immunohistochemistry showed that co-grafts grew, generated new photoreceptors and developed neuronal processes that were integrated into the host retina. This novel approach can be considered as a new therapy for complete replacement of a degenerated retina.
摘要：
终末期年龄相关性黄斑变性(AMD)和色素性视网膜炎(RP)是导致不可逆视力丧失的两种主要视网膜变性(RD)病症。永久性眼睛损伤也可能发生在战场上或由于事故。这表明对于开发治疗永久性视网膜损伤的有效策略存在未满足的需求。在以往的研究中,胎儿视网膜及其视网膜色素上皮（RPE）的共移植片在大鼠视网膜疾病模型和患者中表现出视力改善，但这还没有在干细胞来源的组织中尝试。在这里，我们展示了一种使用“全视网膜贴片”的不可逆视网膜眼损伤的细胞疗法，该“全视网膜贴片”由人造布鲁赫膜（BM）上的视网膜光感受器祖细胞和健康的RPE细胞组成。为此，使用生物粘合剂[明胶，生长因子减少的基质胶，和中等粘度(MVG)藻酸盐]。在视网膜变性晚期的免疫缺陷皇家外科医学院（RCS）大鼠中进行了体内移植实验。基于组织学评估和光学相干断层扫描（OCT）成像观察到严重受损视网膜的结构重建。通过视动行为测试和上丘电生理学进行视觉功能评估。观察到共移植物在大鼠视网膜下间隙中的长期存活和视觉功能的改善。免疫组织化学显示共移植物生长，产生了新的光感受器，并发展了整合到宿主视网膜中的神经元过程。这种新方法可以被认为是完全替代变性视网膜的新疗法。
