4.7 Review

Intraocular in vivo imaging of pancreatic islet cell physiology/pathology

Journal

MOLECULAR METABOLISM
Volume 6, Issue 9, Pages 1002-1009

Publisher

ELSEVIER
DOI: 10.1016/j.molmet.2017.03.014

Keywords

Diabetes mellitus; Type 1 diabetes; Type 2 diabetes; Pancreatic islet; Pancreatic beta cell; Live-cell imaging; Fluorescence microscopy; In vivo imaging; Anterior chamber of the eye

Funding

  1. Karolinska Institutet (KID programme)
  2. Swedish Research Council
  3. Family Erling-Persson Foundation
  4. Novo Nordisk Foundation
  5. Stichting of Jochnick Foundation
  6. Swedish Diabetes Association
  7. Scandia Insurance Company Ltd.
  8. Diabetes Research and Wellness Foundation
  9. Berth von Kantzow's Foundation
  10. Strategic Research Program in Diabetes at Karolinska Institutet
  11. ERC-AdG [338936-BetaImage]
  12. ERC-PoC [727306-BetaScreen]
  13. Swedish Foundation for Strategic Research
  14. Knut and Alice Wallenberg Foundation
  15. Novo Nordisk Fonden [NNF17OC0026726, NNF12OC1016557] Funding Source: researchfish

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Background: Diabetes mellitus has reached epidemic proportions and requires new strategies for treatment. Unfortunately, the efficacy of treatment regimens on maintaining/re-gaining functional beta cell mass can, at the present, only be determined indirectly. Direct monitoring of beta cell mass is complicated by the anatomy of the endocrine pancreas, which consists of thousands to a million of discrete micro-organs, i.e. islets of Langerhans, which are scattered throughout the pancreas. Scope of review: Here, we review the progress made over the last years using the anterior chamber of the eye as a transplantation site for functional imaging of pancreatic islet cells in the living organism. Islets engrafted on the iris are vascularized and innervated and the cornea, serving as a natural body-window, allows for microscopic, non-invasive, longitudinal evaluation of islet/beta cell function and survival with single cell resolution in health and disease. Major conclusions: Data provided by us and others demonstrate the high versatility of this imaging platform. The use of 'reporter islets' engrafted in the eye, reporting on the status of in situ endogenous islets in the pancreas of the same animal, allows the identification of key events in the development and progression of diabetes. This will not only serve as a versatile research tool but will also lay the foundation for a personalized medicine approach and will serve as a screening platform for new drugs and/or treatment protocols. 'Metabolic' islet transplantation, in which islets engrafted in the eye replace the endogenous beta cells, will allow for the establishment of islet-specific transgenic models and 'humanized' mouse models as well as serving as the basis for a new clinical transplantation site for the cure of diabetes. (C) 2017 The Authors. Published by Elsevier GmbH.

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