SUBRETINAL TRANSPLANTATION OF ISLETS OF LANGERHANS

美国至少有一千二百万人患有糖尿病， 微血管并发症。最近的结果 报告的糖尿病控制和并发症试验最终确定 强化胰岛素治疗使血糖接近正常 比传统治疗更有效地预防 以及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， 将提供分钟到分钟的血糖控制， 低血糖发作这种控制可能是可能的， 移植或分离的胰岛移植。分离 胰岛，移植到免疫特权部位， 睾丸，或与宿主的免疫抑制已被证明是 在动物和人类中取得了有限的成功。视网膜下腔 和玻璃体共享前房 角膜和前房相关免疫偏离（ACAID） 的眼睛。拟议研究的目的是：l）确定是否 视网膜下间隙是同种异体移植免疫豁免部位 胰岛移植，2）以确定是否 胰岛的血管再生和存活将得到增强， 与经基因工程改造以产生VEGF的细胞共移植， 3)与支持细胞共同移植， 保护小岛。移植胰岛的长期效果 血糖控制将通过频繁监测血液 葡萄糖水平视网膜功能和结构的任何相关改变 将使用眼底照相，荧光素血管造影， 视网膜电图和组织学及电子显微镜技术。

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.