Intraocular in vivo imaging of pancreatic islet cell physiology/pathology

Abstract

BackgroundDiabetes 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 reviewHere, 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 conclusionsData 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.

Alpha cell regulation of beta cell function

“…5). Transplantation of human islets to the anterior chamber of the eye allows direct observation of various variables of islet morphology and function [69,70]. Furthermore, the exposed location of the islets in the eye allows for manipulation by local treatment or, for that matter, light, and can illustrate, for example, the effects of parasympathetic innervation [23,54].…”

A Review of the Emerging Role of Silk for the Treatment of the Eye

“…The pancreatic islet explant work by Hedhammar and colleagues showed that it is plausible to transplant insulin secreting islet-like clusters from mouse and human primary cells grown on a silk foam into the mouse eye. The transplanted clusters remained capable of releasing insulin ( 80 ) and were vascularised and innervated within the eye ( 81 ).…”

Human Islet Isolation and Distribution Efforts for Clinical and Basic Research

“…Exocytotic events may also be studied using total internal reflection fluorescence (TIRF) microscopy to track individual insulin granule fusion in the beta cells of intact human islets [127,128]. Another approach that facilitates the longitudinal and non-invasive functional imaging of islet cells in an in vivo environment involves the transplantation of isolated human islets into the anterior chamber (AC) of the mouse eye followed by microscopic analysis [129]. This technique allows the engraftment and subsequent innervation and vascularization of islets, at least in rodent models.…”