The eye as a novel imaging site in diabetes research

• Published in: Pharmacology & therapeutics (Oxford) 2019-05, Vol.197, p.103-121
• Main Authors: Yang, Shao-Nian, Berggren, Per-Olof
• Format: Article
• Language: English
• Subjects: Animals; Anterior Chamber - diagnostic imaging; Autoimmune insulitis; Biomedical Research; Diabetes mellitus; Diabetes Mellitus - diagnostic imaging; Humans; In vivo imaging; Insulin resistance; Islets of Langerhans Transplantation; Medicin och hälsovetenskap; Pancreatic islet; The anterior chamber of the eye
• ISSN: 0163-7258; 1879-016X; 1879-016X
• DOI: 10.1016/j.pharmthera.2019.01.005

Diabetes develops due to deficient functional β cell mass, insulin resistance, or both. Yet, various challenges in understanding the mechanisms underlying diabetes development in vivo remain to be overcome owing to the lack of appropriate intravital imaging technologies. To meet these challenges, we have exploited the anterior chamber of the eye (ACE) as a novel imaging site to understand diabetes basics and clinics in vivo. We have developed a technology platform transplanting pancreatic islets into the ACE where they later on can be imaged non-invasively for long time. It turns out that the ACE serves as an optimal imaging site and provides implanted islets with an oxygen-rich milieu and an immune-privileged niche where they undergo optimal engraftment, rich vascularization and dense innervation, preserve organotypic features and live with satisfactory viability and functionality. The ACE technology has led to a series of significant observations. It enables in vivo microscopy of islet cytoarchitecture, function and viability in the physiological context and intravital imaging of a variety of pathological events such as autoimmune insulitis, defects in β cell function and mass and insulin resistance during diabetes development in a real-time manner. Furthermore, application of the ACE technology in humanized mice and non-human primates verifies translational and clinical values of the technology. In this article, we describe the ACE technology in detail, review accumulated knowledge gained by means of the ACE technology and delineate prospective avenues for the ACE technology.