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

被引:36
|
作者
Mojibian, Majid [1 ]
Harder, Brigitte [1 ]
Hurlburt, Andrew [1 ]
Bruin, Jennifer E. [1 ]
Asadi, Ali [1 ]
Kieffer, Timothy J. [1 ,2 ]
机构
[1] Univ British Columbia, Lab Mol & Cellular Med, Dept Cellular & Physiol Sci, Inst Life Sci, Vancouver, BC V6T 1Z3, Canada
[2] Univ British Columbia, Dept Surg, Vancouver, BC V6T 1Z3, Canada
基金
加拿大健康研究院;
关键词
Anterior chamber of the eye; Autoimmune attack; Diabetes; Islets; Transplantation; OCULAR IMMUNE PRIVILEGE; HIGH-RESOLUTION; TRANSPLANTATION; CELLS;
D O I
10.1007/s00125-013-3004-z
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. 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. 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 a parts per thousand yen200 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. 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.
引用
收藏
页码:2213 / 2221
页数:9
相关论文
共 35 条
  • [31] Increased expression of toll-like receptor 4 and inflammatory cytokines, interleukin-6 in particular, in islets from a mouse model of obesity and type 2 diabetes
    Ladefoged, Mette
    Buschard, Karsten
    Hansen, Ann Maria Kruse
    APMIS, 2013, 121 (06) : 531 - 538
  • [32] Compound A attenuates proinflammatory cytokine-induced endoplasmic reticulum stress in beta cells and displays beneficial therapeutic effects in a mouse model of autoimmune diabetes
    Luz Andreone
    Florencia Fuertes
    Carolina Sétula
    Andres E. Barcala Tabarrozzi
    Miranda S. Orellano
    Ricardo A. Dewey
    Rita Bottino
    Karolien De Bosscher
    Marcelo J. Perone
    Cellular and Molecular Life Sciences, 2022, 79
  • [33] Imaging dynamics of CD11c+ cells and Foxp3+ cells in progressive autoimmune insulitis in the NOD mouse model of type 1 diabetes
    Schmidt-Christensen, Anja
    Hansen, Lisbeth
    Ilegems, Erwin
    Fransen-Pettersson, Nina
    Dahl, Ulf
    Gupta, Shashank
    Larefalk, Asa
    Hannibal, Tine D.
    Schulz, Alexander
    Berggren, Per-Olof
    Holmberg, Dan
    DIABETOLOGIA, 2013, 56 (12) : 2669 - 2678
  • [34] Low doses of anti-CD3, ciclosporin A and the vitamin D analogue, TX527, synergise to delay recurrence of autoimmune diabetes in an islet-transplanted NOD mouse model of diabetes
    Baeke, F.
    Van Belle, T. L.
    Takiishi, T.
    Ding, L.
    Korf, H.
    Laureys, J.
    Gysemans, C.
    Mathieu, C.
    DIABETOLOGIA, 2012, 55 (10) : 2723 - 2732
  • [35] Autoreactive T cells induce necrosis and not BCL-2-regulated or death receptor-mediated apoptosis or RIPK3-dependent necroptosis of transplanted islets in a mouse model of type 1 diabetes
    Zhao, Yuxing
    Scott, Nicholas A.
    Fynch, Stacey
    Elkerbout, Lorraine
    Wong, W. Wei-Lynn
    Mason, Kylie D.
    Strasser, Andreas
    Huang, David C.
    Kay, Thomas W. H.
    Thomas, Helen E.
    DIABETOLOGIA, 2015, 58 (01) : 140 - 148