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.
机构:
Univ Copenhagen, Fac Hlth & Med Sci, ISIM Immunol, Copenhagen, Denmark
Lund Univ, BMC, EMV Immunol, S-22184 Lund, SwedenUniv Copenhagen, Fac Hlth & Med Sci, ISIM Immunol, Copenhagen, Denmark
Gupta, Shashank
Larefalk, Asa
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机构:
Umea Univ, Fac Med, Dept Clin Microbiol, Umea, SwedenUniv Copenhagen, Fac Hlth & Med Sci, ISIM Immunol, Copenhagen, Denmark
Larefalk, Asa
Hannibal, Tine D.
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机构:
Univ Copenhagen, Fac Hlth & Med Sci, ISIM Immunol, Copenhagen, Denmark
Lund Univ, BMC, EMV Immunol, S-22184 Lund, SwedenUniv Copenhagen, Fac Hlth & Med Sci, ISIM Immunol, Copenhagen, Denmark
Hannibal, Tine D.
Schulz, Alexander
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机构:
Univ Copenhagen, Imaging Core Facil, Fac Hlth & Med Sci, Frederiksberg, DenmarkUniv Copenhagen, Fac Hlth & Med Sci, ISIM Immunol, Copenhagen, Denmark
Schulz, Alexander
Berggren, Per-Olof
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机构:
Karolinska Inst, Rolf Luft Res Ctr Diabet & Endocrinol, Stockholm, SwedenUniv Copenhagen, Fac Hlth & Med Sci, ISIM Immunol, Copenhagen, Denmark
Berggren, Per-Olof
Holmberg, Dan
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机构:
Univ Copenhagen, Fac Hlth & Med Sci, ISIM Immunol, Copenhagen, Denmark
Lund Univ, BMC, EMV Immunol, S-22184 Lund, Sweden
Umea Univ, Fac Med, Dept Clin Microbiol, Umea, SwedenUniv Copenhagen, Fac Hlth & Med Sci, ISIM Immunol, Copenhagen, Denmark
机构:
St Vincents Inst Med Res, Melbourne, Vic 3065, AustraliaSt Vincents Inst Med Res, Melbourne, Vic 3065, Australia
Zhao, Yuxing
Scott, Nicholas A.
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St Vincents Inst Med Res, Melbourne, Vic 3065, AustraliaSt Vincents Inst Med Res, Melbourne, Vic 3065, Australia
Scott, Nicholas A.
Fynch, Stacey
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St Vincents Inst Med Res, Melbourne, Vic 3065, AustraliaSt Vincents Inst Med Res, Melbourne, Vic 3065, Australia
Fynch, Stacey
Elkerbout, Lorraine
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St Vincents Inst Med Res, Melbourne, Vic 3065, AustraliaSt Vincents Inst Med Res, Melbourne, Vic 3065, Australia
Elkerbout, Lorraine
Wong, W. Wei-Lynn
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机构:
Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, AustraliaSt Vincents Inst Med Res, Melbourne, Vic 3065, Australia
Wong, W. Wei-Lynn
Mason, Kylie D.
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Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia
Univ Melbourne, Dept Med Biol, Melbourne, Vic, AustraliaSt Vincents Inst Med Res, Melbourne, Vic 3065, Australia
Mason, Kylie D.
Strasser, Andreas
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机构:
Univ Melbourne, Dept Med, St Vincents Hosp, Melbourne, Vic, Australia
Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia
Univ Melbourne, Dept Med Biol, Melbourne, Vic, AustraliaSt Vincents Inst Med Res, Melbourne, Vic 3065, Australia
Strasser, Andreas
Huang, David C.
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Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia
Univ Melbourne, Dept Med Biol, Melbourne, Vic, AustraliaSt Vincents Inst Med Res, Melbourne, Vic 3065, Australia
Huang, David C.
Kay, Thomas W. H.
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St Vincents Inst Med Res, Melbourne, Vic 3065, Australia
Univ Melbourne, Dept Med, St Vincents Hosp, Melbourne, Vic, AustraliaSt Vincents Inst Med Res, Melbourne, Vic 3065, Australia
Kay, Thomas W. H.
Thomas, Helen E.
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St Vincents Inst Med Res, Melbourne, Vic 3065, Australia
Univ Melbourne, Dept Med, St Vincents Hosp, Melbourne, Vic, AustraliaSt Vincents Inst Med Res, Melbourne, Vic 3065, Australia