SUBRETINAL TRANSPLANTATION OF ISLETS OF LANGERHANS

美国至少有1200万人患有糖尿病，而且 易受微血管并发症的影响。最近的结果是 已报道的糖尿病控制和并发症试验最终确定成立 在血糖接近正常的情况下进行强化胰岛素治疗 在预防疾病方面明显比传统疗法更有效 减缓糖尿病视网膜病变和其他疾病的发展 微血管并发症。然而，糖尿病的理想治疗方法是， 将提供每分钟的血糖控制，而不会有 低血糖发作。这样的控制可能通过胰腺来实现 孤立的朗格汉斯胰岛的移植或移植。孤立 朗格汉斯的胰岛，移植到免疫特权部位，如 睾丸，或有免疫抑制的宿主已被证明是 在动物和人类身上取得了有限的成功。视网膜下间隙 眼球和玻璃体最近被显示为共用前房 角膜和前房相关免疫偏离(ACAID) 眼睛的。拟议研究的目的是为了确定L)是否 视网膜下间隙是同种异体免疫的特免区 朗格汉斯胰岛移植，2)确定 如果胰岛血管重新血运重建和存活将得到加强 与经过基因工程的细胞共同移植以制造血管内皮生长因子或 3)与支持细胞共同移植，将提供免疫 保护小岛。胰岛移植的远期疗效观察 血糖控制将通过频繁监测血液来确定 血糖水平。任何与视网膜功能和结构相关的改变 将通过眼底照相，荧光素血管造影术， 视网膜电描记术、组织学和电子显微镜技术。

At least twelve million people in the United States have diabetes and are subject to its microvascular complications. The results of the recently reported Diabetes Control and Complications Trial definitively established that intensive insulin treatment with near-normalization of blood glucose is significantly more effective than conventional treatment in preventing and slowing the development of diabetic retinopathy and other microvascular complications. The ideal treatment for diabetes, however, would provide minute-to-minute blood glucose control without danger of hypoglycemic episodes. Such control might be possible with pancreatic transplant or transplantation of isolated islets of Langerhans. Isolated islets of Langerhans, transplanted in an immune privileged site such as the testis, or with immunosuppression of the host have been shown to be successful in animals and humans to a limited extent. The subretinal space and vitreous of the eye have recently been shown to share anterior chamber associated immune deviation (ACAID) with the cornea and anterior chamber of the eye. The purposes of the proposed studies are to l) determine if the subretinal space is an immune privileged site for allogenic transplantation of islets of Langerhans, 2) to determine if revascularization and survival of islets will be enhanced if they are cotransplanted with cells that are genetically engineered to make VEGF or 3) cotransplanted with Sertoli cells that will provide immunological protection of the islets. The long-term effect of transplanted islets on blood glucose control will be determined by frequent monitoring of blood glucose levels. Any related alterations in retinal function and structure will be determined using fundus photography, fluorescein angiography, electroretinography and histological and electron microscopic techniques.