Non-invasive in vivo imaging and methods for treating diabetes
Inventors
Berggren, Per-Olof • Caicedo, Alejandro
Assignees
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Publication Number
US-10493108-B2
Publication Date
2019-12-03
Expiration Date
Abstract
The present invention provides novel drug discovery platforms and methods for treating diabetes.
Core Innovation
The invention provides a non-invasive in vivo drug discovery and diabetes treatment platform using cornea-accessible fluorescence imaging. Fluorescently labeled target cells are engrafted into the anterior chamber of an animal’s eye, and test compounds are contacted with the engrafted cells. Compound-induced changes are detected using fluorescence imaging, including 2-photon confocal approaches, to assess changes in labeled cell activity, location, and amount over time.
The disclosed platform is applied to diabetes by transplanting insulin-producing cells into the eye to promote insulin production. The target insulin-producing cells include isolated pancreatic islets and isolated pancreatic β cells. The platform supports monitoring related biological outcomes longitudinally, including measures associated with insulin-producing cell function and viability after injury.
Supporting disclosure includes anterior-chamber islet engraftment and vascularization, followed by longitudinal imaging of β-cell function and β-cell death. The described approach emphasizes cornea as a natural body window for repeated, non-invasive fluorescence imaging readouts.
Claims Coverage
The partial content supports one independent claim directed to diabetes treatment by transplanting insulin-producing cells onto the iris of an eye. The independent claim is further narrowed by dependent claims specifying whether the insulin-producing cells are present in an isolated pancreatic islet or comprise isolated pancreatic β cells, and by dependent claims specifying restoring normoglycemia.
Diabetes treatment by iris transplantation of insulin-producing cells
A method for treating a subject with diabetes by transplanting onto the iris of an eye of a subject with diabetes an amount effective of insulin-producing cells to promote insulin production, wherein the insulin-producing cells are present in an isolated pancreatic islet or comprise isolated pancreatic β cells.
Insulin-producing cells present in an isolated pancreatic islet
The method further specifies that the insulin-producing cells are present in an isolated pancreatic islet.
Insulin-producing cells comprise isolated pancreatic β cells
The method is characterized in that the insulin-producing cells comprise isolated pancreatic β cells.
Restoring normoglycemia
The method of claim 1 is further defined such that the treating comprises restoring normoglycemia.
Across the supported independent claim and its dependents, the core claim coverage centers on transplanting an amount effective of insulin-producing cells onto the iris to promote insulin production, with explicit cell-source distinctions between isolated pancreatic islets and isolated pancreatic β cells, and with an outcome requirement of restoring normoglycemia.
Stated Advantages
Non-invasive in vivo fluorescence imaging for monitoring labeled target cells in the anterior chamber of an eye.
Longitudinal detection of compound-induced changes in labeled cell activity, location, and amount.
Supports diabetes treatment by promoting insulin production via transplantation of insulin-producing cells to the eye.
Enables monitoring of β-cell function longitudinally and non-invasive longitudinal imaging of β-cell death.
Documented Applications
Diabetes treatment (type I diabetes) by transplanting insulin-producing cells into the eye to promote insulin production.
Drug discovery/drug development using cornea-accessible fluorescence imaging to detect compound-induced changes in labeled cell activity, location, and amount.
Monitoring β-cell function in vivo via Ca2+ dynamics in response to glibenclamide.
Monitoring β-cell death in vivo via annexin V-APC after alloxan-induced injury.
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