Stem cell based treatment strategy for Age-related Macular Degeneration (AMD)

视网膜变性是一组致盲性疾病，越来越多地影响加州人的健康和福祉。据估计，到2020年，超过450，000加利福尼亚人将因年龄相关性黄斑变性（AMD）而视力丧失或失明，AMD是老年人视网膜变性疾病的最常见原因。AMD是一种进行性眼部疾病，视网膜的一部分，称为黄斑，使人们能够阅读，可视化面部和驾驶。这种疾病最初会导致中心视力的扭曲，最终导致法律的失明。在眼睛后面的一层细胞称为视网膜色素上皮细胞（RPE），为视网膜的感光细胞提供支持，保护和营养;光感受器由杆和锥组成。这些RPE细胞的功能障碍和/或丧失在PR？因此，AMD的失明。通过对受损的视网膜色素上皮细胞和视网膜细胞进行适当的置换，可以达到有效的治疗效果。更具体地说，再生和恢复的RPE层将防止PR的不可逆损失？S.然而，由于缺乏一种可行的方法来恢复RPE细胞，阻碍了这一潜在疗法的实现，人类胚胎干细胞（human embryonic stem cells，hES）知识和技术的最新进展为细胞替代疗法的发展带来了新的希望。hES细胞能够无限的自我复制和产生不同的细胞类型。hES细胞衍生的RPE细胞是一种潜在的、无限的、强大的再生RPE的来源，我们假设通过移植功能极化的hES细胞衍生的RPE单层来再生和恢复RPE，可以克服RPE的功能障碍和/或丧失。这种从hES中提取的RPE细胞可以通过微创手术移植到眼睛中，挽救PR免于死亡。我们的团队由独特的多学科成员组成，他们在盲人恢复视力以及视网膜细胞移植和干细胞研究方面拥有超过二十年的经验。我们的计划是利用我们的专业知识和基础设施，向FDA展示我们使用hES衍生的RPE细胞进行的临床前试验的成功，以获得批准在因AMD而有视力丧失风险的患者中进行临床试验。

Retinal degeneration represents a group of blinding diseases that are increasingly impacting the health and well being ofCalifornians. It is estimated that by 2020, over 450,000 Californians will suffer from vision loss or blindness due to the age-relatedmacular degeneration (AMD), the most common cause of retinal degeneration diseases in the elderly. AMD is a progressiveocular disease of the part of the retina, called the macula, which enables people to read, visualize faces, and drive. The diseaseinitially causes distortion in central vision, and eventually leads to legal blindness.A layer of cells at the back of the eye called the retinal pigment epithelium (RPE), provide support, protection, and nutrition tothe light sensitive cells of the retina; the photoreceptors which consist of rods and cones . The dysfunction and/or loss of theseRPE cells play a critical role in the loss of the PR?s and hence the blindness in AMD. Effective treatment could be achieved byproper replacement of damaged RPE and retinal cells with healthy ones. More specifically, the regenerated and restored RPElayer would prevent the irreversible loss of the PR?s. However, the lack of a feasible approach to restore the RPE cells hasprevented the realization of a potential therapy.Recent advances in knowledge and technology of human embryonic stem (hES) cells brings new hope for the development ofcell replacement treatment. hES cells are capable of unlimited self-replication and production of different cell types. RPE cellsderived from hES cells are a potentially unlimited and robust source for regenerating RPE.We hypothesize that the dysfunction and/or loss of RPE can be overcome by regenerating and restoring the RPE through thetransplantation of functionally polarized RPE monolayers derived from hES cells. Such RPE cells derived from hES can then betransplanted into the eye, using minimally invasive surgical procedures saving the PR from dying.Our group is composed of unique multidisciplinary members who collectively have more than two decades of experience inefforts to restore sight to the blind as well as retinal cell transplantation and stem cell research. Our plan for this grant is to useour expertise and infrastructure to show to the FDA the success of our preclinical tests using hES derived RPE cells in order to getapproval to conduct a clinical trial in patients at risk of vision loss due to AMD.Limit Public