SUBRETINAL TRANSPLANTATION OF ISLETS OF LANGERHANS

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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.