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

视网膜变性是一组致盲疾病，正日益影响加州人的健康和福祉。据估计，到2020年，超过45万加州人将因老年性黄斑变性（AMD）而丧失视力或失明，这是老年人视网膜变性疾病的最常见原因。老年性黄斑变性是视网膜黄斑部分的一种进行性眼部疾病，黄斑使人们能够阅读、看到面孔和驾驶。这种疾病最初会导致中央视力扭曲，最终导致法定失明。眼睛后部的一层细胞称为视网膜色素上皮（RPE），为视网膜的光敏细胞提供支持、保护和营养；由杆状和锥状细胞组成的光感受器。这些erpe细胞的功能障碍和/或丢失在PR？从而导致AMD的失明。适当替换受损的RPE和视网膜细胞可获得有效的治疗。更具体地说，再生和修复的RPElayer可以防止PR的不可逆转损失。然而，缺乏一种可行的方法来恢复RPE细胞，阻碍了潜在治疗的实现。近年来人类胚胎干细胞知识和技术的进步为细胞替代治疗的发展带来了新的希望。hES细胞能够无限地自我复制并产生不同类型的细胞。来自hES细胞的RPE细胞是再生RPE的潜在无限和强大的来源。我们假设，通过移植来自hES细胞的功能性极化RPE单层膜来再生和恢复RPE，可以克服RPE功能障碍和/或缺失。这种来自he细胞的RPE细胞可以移植到眼睛中，使用微创外科手术挽救PR免于死亡。我们的小组由独特的多学科成员组成，他们共同拥有超过二十年的经验，致力于盲人恢复视力以及视网膜细胞移植和干细胞研究。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细胞进行临床前试验的成功，以便获得批准在有因AMD导致视力丧失风险的患者中进行临床试验。限制公众

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