Islet Transplantation to the Anterior Chamber of the Eye-A Future Treatment Option for Insulin-Deficient Type-2 Diabetics? A Case Report from a Nonhuman Type-2 Diabetic Primate
Islet Transplantation to the Anterior Chamber of the Eye-A Future Treatment Option for Insulin-Deficient Type-2 Diabetics? A Case Report from a Nonhuman Type-2 Diabetic Primate
复制标题
DOI：
10.1177/0963689720913256
复制
发表时间：
2020-01-01
影响因子：
3.3
通讯作者：
Berggren, Per-Olof
中科院分区：
文献类型：
--
作者：
Tun, Sai Bo Bo;Chua, Minni;Berggren, Per-Olof
通过将胰岛移植到肝脏来替代分泌胰岛素的β细胞是治疗1型糖尿病的一种很有前途的方法。然而，低氧张力、剪切应力和炎症诱导导致胰岛功能障碍和损失。眼前房（ACE）因其可及性、高氧压和免疫特权环境而获得了相当大的兴趣，并代表了一种替代的治疗性胰岛移植部位。我们之前已经在小鼠和非人类灵长类1型糖尿病模型中证明了眼内胰岛移植的可行性，现在正在评估其对非人类灵长类2型糖尿病模型中葡萄糖稳态的功效。我们将异体供体胰岛（1,500胰岛当量/kg）移植到患有高脂肪饮食诱导的2型糖尿病的食蟹猴一只眼睛的前房。对双眼前后段进行反复检查，以监测移植的胰岛并评估整体眼部健康状况。常规评估空腹血糖水平、血液生化和其他代谢参数，以确定胰岛移植的功能和糖尿病状态。移植的胰岛在移植1个月后迅速移植到虹膜上并血管化。我们没有发现眼压、白内障形成、眼炎或视网膜血管变形的变化。移植时空腹血糖水平明显降低，并且移植逆转了糖尿病的进展。代谢指标血红蛋白A（1C）和果糖胺在胰岛移植后得到改善。综上所述，短期测量和长期代谢指标表明，一只患有2型糖尿病的食蟹猴眼内胰岛移植改善了其整体血浆葡萄糖稳态。这些结果进一步支持ACE作为2型糖尿病患者临床胰岛移植的替代部位的未来应用。
Replacement of the insulin-secreting beta cells through transplantation of pancreatic islets to the liver is a promising treatment for type-1 diabetes. However, low oxygen tension, shear stress, and the induction of inflammation lead to significant islet dysfunction and loss. The anterior chamber of the eye (ACE) has gained considerable interest and represents an alternative therapeutic islet transplantation site because of its accessibility, high oxygen tension, and immune-privileged milieu. We have previously demonstrated the feasibility of intraocular islet transplant in mouse and nonhuman primate models of type-1 diabetes and are now assessing its efficacy on glucose homeostasis in a nonhuman primate model of type-2 diabetes. We transplanted allogeneic donor islets (1,500 islet equivalents/kg) into the anterior chamber of one eye in a cynomolgus monkey with high-fat-diet-induced type-2 diabetes. Repeated examinations of the anterior and posterior segments of both eyes were done to monitor the engrafted islets and assess the overall ocular health. Fasting blood glucose level, blood biochemistry, and other metabolic parameters were routinely evaluated to determine the function of the islet graft and diabetes status. The transplanted islets were rapidly engrafted onto the iris and became vascularized 1 month after transplantation. We did not detect changes in intraocular pressure, cataract formation, ophthalmitis, or retinal vessel deformation. A significant lower fasting blood glucose level was observed while the graft was in place, and the transplantation reverts the progression of diabetes. The metabolic markers, hemoglobin A(1C) and fructosamine, demonstrated improvement following islet transplantation. As a conclusion, intraocular islet transplantation in one eye of a cynomolgus monkey with type-2 diabetes improved its overall plasma glucose homeostasis, as evidenced by short-term measures and long-term metabolic markers. These results further support the future application of the ACE as an alternative site for clinical islet transplants in the context of type-2 diabetes.