Macular regeneration

Age-related macular degeneration (AMD) is the leading cause of blindness in the population over 60 in the western world. There are two clinical forms of AMD: dry and wet. The initial damage of AMD is the dysfunction of the retinal pigment epithelial (RPE) cells and the underlying supportive Bruch’s membrane, which results in the dysfunction or loss of photoreceptors. Subsequently the patients undergo blindness. Currently there is no therapy for the dry AMD which accounts for the majority of the cases (~90%). Cell-based therapy, replacing the damaged cells in the retina, is the most promising treatment. Our rationale is to engineer a therapeutic intact functional RPE monolayer derived from human stem cells on the prosthetic Bruch’s membrane ready for subretinal implantation in order to restore the vision. We are able to develop a 3-dimensional nanofibrous membrane with surface modification which mimics the natural human Bruch’s membrane. The prosthetic Bruch’s membrane is made of FDA approved polymer which gives advantages for clinical application. A long-term functional RPE monolayer has been engineered on such substrate and is ready for subretinal implantation to investigate its potential of visual improvement. A further step is to develop a retinal multilayer consisting of the photoreceptors and RPE, which can benefit not only the AMD but also the other retinal diseases.

年龄相关性黄斑变性（Age-related macular degeneration, AMD）是西方社会60岁以上人群失明的首要病因。该病存在两种临床分型：干性与湿性。AMD的初始病理损伤为视网膜色素上皮（Retinal Pigment Epithelial, RPE）细胞及下方起支持作用的布鲁赫膜（Bruch’s membrane）功能异常，进而引发光感受器功能障碍或丢失，最终导致患者失明。目前占总病例约90%的干性AMD尚无有效治疗手段，以替换视网膜受损细胞为目标的细胞治疗是当前最具前景的治疗方案。本研究的核心理念为：在人工合成的布鲁赫膜支架上构建源自人类干细胞的治疗性完整功能性RPE单层，用于视网膜下植入以恢复患者视力。我们已成功开发出经表面修饰的三维纳米纤维膜，可模拟天然人类布鲁赫膜的结构与功能；该人工布鲁赫膜采用美国食品药品监督管理局（Food and Drug Administration, FDA）批准的聚合物制备，具备良好的临床应用潜力。我们已在该支架上构建出可长期维持功能的RPE单层，目前已准备开展视网膜下植入实验，以验证其改善视力的潜力。后续研究将进一步构建包含光感受器与RPE的视网膜多层结构，该技术不仅可用于AMD的治疗，还可惠及其他视网膜疾病患者。