Non-invasive in vivo imaging and methods for treating type I diabetes
Inventors
Berggren, Per-Olof • Caicedo, Alejandro
Assignees
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Publication Number
US-9463205-B2
Publication Date
2016-10-11
Expiration Date
Abstract
The present invention provides novel drug discovery platforms and methods for treating type I diabetes.
Core Innovation
The patent describes non-invasive in vivo fluorescence drug discovery and monitoring of diabetes-related cell activity using cell engraftment in the anterior chamber of the eye. An isolated pancreatic islet or isolated pancreatic islet cell is transplanted onto the iris, and fluorescently labeled cells are used so that changes in labeled cellular activity, location, or amount are detected by non-invasive imaging. The approach uses fluorescence imaging to visualize cellular behavior over time in the living subject.
The patent states that transplantation of insulin-producing cells into the eye promotes insulin production for treating type I diabetes. The document associates anterior-chamber islet engraftment with maintenance of insulin/glucagon composition and describes restoration of normoglycemia and glucose tolerance responses in streptozotocin-diabetic mice. The eye-based engraftment window enables longitudinal observation of vascular and cellular changes at single-cell resolution using fluorescence microscopy techniques.
The patent further describes longitudinal imaging readouts of functional and injury-related cellular processes. It reports revascularization monitored by imaging of vessel vascularization using Texas Red dextran, and pancreatic β-cell functional signaling monitored by ratiometric Ca2+ imaging using Fluo-4 and Fura-Red in response to glibenclamide. It also reports non-invasive longitudinal monitoring of β-cell death using annexin V-APC after alloxan-induced injury.
Claims Coverage
The claim set covers 3 inventive features centered on treating type I diabetes by transplanting isolated pancreatic tissue onto the iris of the eye and, in one feature, using injection through the cornea.
Transplanting an isolated pancreatic islet onto the iris to promote insulin production
Transplanting onto the iris of the eye of a subject with type I diabetes an amount effective of an isolated pancreatic islet to promote insulin production.
Transplanting an isolated pancreatic islet cell onto the iris to promote insulin production
Transplanting onto the iris of the eye of a subject with type I diabetes an amount effective of an isolated pancreatic islet cell to promote insulin production.
Iris transplantation by injecting through the cornea
Transplantation onto the iris of the eye is performed by injection through the cornea.
The claim set centers on treating type I diabetes by transplanting an amount effective of an isolated pancreatic islet or isolated pancreatic islet cell onto the iris of the eye to promote insulin production, with refinement of whether islets or islet cells are used and the delivery route via injection through the cornea.
Stated Advantages
Promotes insulin production in the subject with type I diabetes.
Restores normoglycemia and glucose tolerance responses in streptozotocin-diabetic mice.
Enables non-invasive longitudinal fluorescence imaging of cellular activity and location/amount.
Enables longitudinal monitoring of revascularization.
Enables functional β-cell signaling readouts using ratiometric Ca2+ imaging.
Enables non-invasive longitudinal monitoring of β-cell death.
Documented Applications
Treating type I diabetes by transplanting an amount effective of an isolated pancreatic islet or isolated pancreatic islet cell onto the iris of the eye to promote insulin production.
Non-invasive in vivo fluorescence drug discovery by transplanting labeled cells, contacting with test compounds, and imaging compound-induced changes.
Longitudinal monitoring of revascularization in engrafted islets using fluorescence imaging.
Monitoring functional β-cell signaling in response to glibenclamide using ratiometric Ca2+ imaging.
Non-invasive longitudinal monitoring of β-cell death after alloxan-induced injury using annexin V-APC.
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