The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
Pharmacol Ther. 2019 May;197:103-121. doi: 10.1016/j.pharmthera.2019.01.005. Epub 2019 Jan 22.
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.
糖尿病的发生是由于功能性β细胞数量减少、胰岛素抵抗或两者共同作用所致。然而,由于缺乏适当的活体成像技术,在理解糖尿病发生的机制方面仍然存在各种挑战。为了应对这些挑战,我们利用眼前房(ACE)作为一种新的成像部位,来在体内理解糖尿病的基础和临床问题。我们开发了一种将胰岛移植到 ACE 的技术平台,使它们可以在那里进行长时间的非侵入性成像。事实证明,ACE 是一个理想的成像部位,为植入的胰岛提供富含氧气的环境和免疫特权微环境,使它们能够进行最佳的移植、丰富的血管生成和密集的神经支配,保持器官样特征,并具有令人满意的活力和功能。ACE 技术带来了一系列重要的观察结果。它能够在生理环境下对胰岛细胞结构、功能和活力进行活体显微镜观察,并实时对各种病理事件进行活体成像,如自身免疫性胰岛炎、β细胞功能和数量缺陷以及糖尿病发展过程中的胰岛素抵抗。此外,ACE 技术在人源化小鼠和非人类灵长类动物中的应用验证了该技术的转化和临床价值。本文详细描述了 ACE 技术,回顾了通过 ACE 技术获得的知识积累,并描绘了 ACE 技术的未来发展方向。