Noninvasive high-resolution in vivo imaging of cell biology in the anterior chamber of the mouse eye

Speier, Stephan; Nyqvist, Daniel; Köhler, Martin; Caicedo, Alejandro; Leibiger, Ingo B.; Berggren, Per Olof

doi:10.1038/nprot.2008.118

Cited by 134 publications

(194 citation statements)

References 24 publications

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“…Even using near-infrared contrast agents or tissue-specific bioluminescence [10][11][12], these techniques are not able to attain single-cell-level sensitivity [14]. The anterior chamber of the eye has been a popular transplantation site for decades [15], as transplanted tissue is readily vascularised and innervated by the iris [16] and the graft can be visualised noninvasively. As such, specific techniques have been developed for transplantation and imaging of transplanted tissue in the eye [16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Implanted islets in the anterior chamber of the eye are prone to autoimmune attack in a mouse model of diabetes

et al. 2013

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Aims/hypothesis Type 1 diabetes is an autoimmune disease resulting from the destruction of insulin-producing beta cells. Along with advances in generating replacement beta cells for treating diabetes, there is also increasing demand for non-invasive tools to evaluate the recurrence of autoimmune attack on transplanted tissue. Here, we examined the anterior chamber of the eye as a potential islet transplant site, and also evaluated whether in vivo imaging of the islets transplanted in the eye could enable real-time visualisation of autoimmune processes underway in the pancreas. Methods Syngeneic islet equivalents were transplanted into the eye or kidney capsule of streptozotocin-induced diabetic C57BL/6 mice to compare islet dose (25-125 islet equivalents) and function across transplant sites. Autoimmune attack of syngeneic islets was evaluated in the pancreas and eye tissues of NOD and NOD-severe combined immunodeficient (SCID) mice given diabetogenic splenocytes. Results Islet transplantation in the eye decreased fasting plasma glucose levels and increased weight gain and survival in an islet-dose-dependent manner. Even 50 islets in the eye reduced blood glucose levels, whereas ≥200 islets were required in the kidney for a similar effect. Autoimmune destruction of pancreatic islets in the eye mirrored that in the pancreas and could be visualised in real time by noninvasive imaging. Conclusions/interpretation We found that far fewer islets were required to restore normoglycaemia when transplanted into the anterior chamber of the eye vs the kidney capsule. However, our results suggest that islets are not protected against autoimmune attack in the eye, making this a suitable site for visualising autoimmune processes against transplanted tissue.

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Section: Introductionmentioning

confidence: 99%

Implanted islets in the anterior chamber of the eye are prone to autoimmune attack in a mouse model of diabetes

et al. 2013

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“…Thus, understanding the regulation of function and survival and assessing the clinical outcome of individual treatment strategies for diabetes requires a monitoring system that can continuously report on the status of the endocrine pancreas in the living organism. We have developed a technical platform for noninvasive, longitudinal, in vivo imaging at single-cell resolution (2,3). In the present study, we applied this in vivo imaging technique to test our hypothesis that islets transplanted into the anterior chamber of the eye can report on the functional status of the endogenous endocrine pancreas, and that intervention with pathological processes in the islets of Langerhans can be monitored in the eye.…”

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confidence: 99%

Reporter islets in the eye reveal the plasticity of the endocrine pancreas

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Speier

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Significance An adaptive plasticity of the insulin-secreting pancreatic beta cells, located in the islets of Langerhans, is essential for maintaining proper blood glucose homeostasis under various functional demands. Understanding the molecular mechanisms underlying the regulation of beta cell mass and function is critically dependent on an in vivo monitoring system that can continuously report on the functional status of the islets. Because direct inspection of these islets is obstructed due to the fact that they are deeply embedded and scattered within the pancreas, we propose the use of “reporter islets” transplanted into the anterior chamber of the eye, serving as optically accessible indicators of islet plasticity in the pancreas and as a tool to individually assess effectiveness of specific treatment regimens.

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“…Microscopy The in vivo imaging set-up was as previously described [3,4]. To visualise blood vessels in vivo, dextran labelled with Texas Red (100 μl of 10 mg/ml; Molecular Probes, Eugene, OR, USA) was injected into the tail vein.…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, as the cornea is a natural body window for non-invasive, longitudinal, in vivo three-dimensional imaging, we are able to study beta cell differentiation and maturation in a living animal. Our approach combines powerful highresolution confocal microscopy with intraocular transplantation to enable non-invasive monitoring of the same individual pancreatic bud longitudinally with the potential for direct biological/pharmacological manipulation of the local environment in the ACE [4] to identify key regulatory mechanisms and factors involved in pancreatic islet development.…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

“…Our inability to visualise islets as they develop over time in vivo needs to be addressed so as to better understand this intricate process. A promising candidate site, not explored in islet development, is the anterior chamber of the eye (ACE) [3,4]. Islets transplanted into the ACE maintain euglycaemia in streptozotocin-treated mouse models of diabetes, and in these mice hyperglycaemia only ensues upon enucleation (eye removal) [3].…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

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The anterior chamber of the eye is a transplantation site that supports and enables visualisation of beta cell development in mice

et al. 2016

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Aims/hypothesis In vivo imaging of the developing pancreas is challenging due to the inaccessibility of the tissue. To circumvent this, on embryonic day 10.5 (E10.5) we transplanted a mouse developing pancreatic bud into the anterior chamber of the eye (ACE) to determine whether the eye is a useful transplant site to support pancreas development. Methods We transplanted an E10.5 dorsal pancreatic bud into the ACE of a syngeneic recipient mouse. Using a mouse insulin promoter-green fluorescent protein (MIP-GFP) mouse as the tissue donor, we non-invasively imaged the pancreatic bud as it develops at single beta cell resolution across time.Results The transplanted pancreatic bud rapidly engrafts and vascularises when transplanted into the ACE. The pancreatic progenitor cells differentiate into exocrine and endocrine cells, including cells expressing insulin, glucagon and somatostatin. The morphology of the transplanted pancreatic bud resembles that of the native developing pancreas. Beta cells within the transplanted pancreatic bud respond to glucose in a manner similar to that of native fetal beta cells and superior to that of in vitro developed beta cells. Unlike in vitro grown pancreatic explants, pancreatic tissue developing in the ACE is vascularised, providing the developing pancreatic tissue with a milieu resembling the native situation. Conclusions/interpretation Altogether, we show that the ACE is able to support growth, differentiation and function of a developing pancreatic bud across time in vivo.

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Noninvasive high-resolution in vivo imaging of cell biology in the anterior chamber of the mouse eye

Cited by 134 publications

References 24 publications

Implanted islets in the anterior chamber of the eye are prone to autoimmune attack in a mouse model of diabetes

Implanted islets in the anterior chamber of the eye are prone to autoimmune attack in a mouse model of diabetes

Reporter islets in the eye reveal the plasticity of the endocrine pancreas

The anterior chamber of the eye is a transplantation site that supports and enables visualisation of beta cell development in mice

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