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在糖尿病的小鼠模型中,植入眼睛前房的胰岛容易受到自身免疫攻击。

Implanted islets in the anterior chamber of the eye are prone to autoimmune attack in a mouse model of diabetes.

机构信息

Laboratory of Molecular and Cellular Medicine, Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.

出版信息

Diabetologia. 2013 Oct;56(10):2213-21. doi: 10.1007/s00125-013-3004-z. Epub 2013 Aug 11.

Abstract

AIMS/HYPOTHESIS: Type 1 diabetes is an autoimmune disease resulting from the destruction of insulin-producing beta cells. Along with advances in generating replacement beta cells for treating diabetes, there is also increasing demand for non-invasive tools to evaluate the recurrence of autoimmune attack on transplanted tissue. Here, we examined the anterior chamber of the eye as a potential islet transplant site, and also evaluated whether in vivo imaging of the islets transplanted in the eye could enable real-time visualisation of autoimmune processes underway in the pancreas.

METHODS

Syngeneic islet equivalents were transplanted into the eye or kidney capsule of streptozotocin-induced diabetic C57BL/6 mice to compare islet dose (25-125 islet equivalents) and function across transplant sites. Autoimmune attack of syngeneic islets was evaluated in the pancreas and eye tissues of NOD and NOD-severe combined immunodeficient (SCID) mice given diabetogenic splenocytes.

RESULTS

Islet transplantation in the eye decreased fasting plasma glucose levels and increased weight gain and survival in an islet-dose-dependent manner. Even 50 islets in the eye reduced blood glucose levels, whereas ≥ 200 islets were required in the kidney for a similar effect. Autoimmune destruction of pancreatic islets in the eye mirrored that in the pancreas and could be visualised in real time by non-invasive imaging.

CONCLUSIONS/INTERPRETATION: We found that far fewer islets were required to restore normoglycaemia when transplanted into the anterior chamber of the eye vs the kidney capsule. However, our results suggest that islets are not protected against autoimmune attack in the eye, making this a suitable site for visualising autoimmune processes against transplanted tissue.

摘要

目的/假设:1 型糖尿病是一种自身免疫性疾病,由产生胰岛素的β细胞破坏引起。随着用于治疗糖尿病的替代β细胞的生成技术的进步,人们对评估移植组织自身免疫攻击复发的非侵入性工具的需求也在不断增加。在这里,我们检查了眼前房作为潜在的胰岛移植部位,并评估了在眼睛中移植的胰岛的体内成像是否能够实时可视化正在进行的胰腺自身免疫过程。

方法

将同基因胰岛等同物移植到链脲佐菌素诱导的糖尿病 C57BL/6 小鼠的眼睛或肾包膜中,以比较移植部位的胰岛剂量(25-125 胰岛等同物)和功能。在给予致糖尿病脾细胞的 NOD 和 NOD-严重联合免疫缺陷(SCID)小鼠中,评估了同种异体胰岛在胰腺和眼睛组织中的自身免疫攻击。

结果

胰岛在眼睛中的移植以胰岛剂量依赖性的方式降低空腹血糖水平并增加体重增加和存活率。即使在眼睛中移植 50 个胰岛也能降低血糖水平,而在肾脏中则需要≥200 个胰岛才能达到类似效果。在眼睛中胰岛的自身免疫破坏与胰腺中的情况相吻合,并且可以通过非侵入性成像实时可视化。

结论/解释:我们发现,当移植到眼前房时,恢复正常血糖所需的胰岛数量比移植到肾包膜时要少得多。然而,我们的结果表明,胰岛在眼睛中不能免受自身免疫攻击,这使得该部位成为可视化针对移植组织的自身免疫过程的合适部位。

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