Differential Responses of Neural Retina Progenitor Populations to Chronic Hyperglycemia.

Diabetic retinopathy is a frequent complication of longstanding diabetes, which comprises a complex interplay of microvascular abnormalities and neurodegeneration. Zebrafish harboring a homozygous mutation in the pancreatic transcription factor display a diabetic phenotype with survival into adulthood, and are therefore uniquely suitable among zebrafish models for studying pathologies associated with persistent diabetic conditions. We have previously shown that, starting at three months of age, mutants exhibit not only vascular but also neuro-retinal pathologies manifesting as photoreceptor dysfunction and loss, similar to human diabetic retinopathy.

Insulin-producing β-cells regenerate ectopically from a mesodermal origin under the perturbation of hemato-endothelial specification.

To investigate the role of the vasculature in pancreatic β-cell regeneration, we crossed a zebrafish β-cell ablation model into the avascular mutant (i.e. ).

Photoreceptor Degeneration Accompanies Vascular Changes in a Zebrafish Model of Diabetic Retinopathy.

Purpose: Diabetic retinopathy (DR) is a leading cause of vision impairment and blindness worldwide in the working-age population, and the incidence is rising. Until now it has been difficult to define initiating events and disease progression at the molecular level, as available diabetic rodent models do not present the full spectrum of neural and vascular pathologies. Zebrafish harboring a homozygous mutation in the pancreatic transcription factor pdx1 were previously shown to display a diabetic phenotype from larval stages through adulthood.

Tcf7l2 plays pleiotropic roles in the control of glucose homeostasis, pancreas morphology, vascularization and regeneration.

Type 2 diabetes (T2D) is a disease characterized by impaired insulin secretion. The Wnt signaling transcription factor Tcf7l2 is to date the T2D-associated gene with the largest effect on disease susceptibility. However, the mechanisms by which TCF7L2 variants affect insulin release from β-cells are not yet fully understood.

, cells are developmentally maintained progenitors for exocrine regeneration following extreme loss of acinar cells in zebrafish larvae.

The exocrine pancreas displays a significant capacity for regeneration and renewal. In humans and mammalian model systems, the partial loss of exocrine tissue, such as after acute pancreatitis or partial pancreatectomy induces rapid recovery via expansion of surviving acinar cells. In mouse it was further found that an almost complete removal of acinar cells initiates regeneration from a currently not well-defined progenitor pool.

Artemisinins Target GABA Receptor Signaling and Impair α Cell Identity.

Type 1 diabetes is characterized by the destruction of pancreatic β cells, and generating new insulin-producing cells from other cell types is a major aim of regenerative medicine. One promising approach is transdifferentiation of developmentally related pancreatic cell types, including glucagon-producing α cells. In a genetic model, loss of the master regulatory transcription factor Arx is sufficient to induce the conversion of α cells to functional β-like cells.

Diabetic pdx1-mutant zebrafish show conserved responses to nutrient overload and anti-glycemic treatment.

Diabetes mellitus is characterized by disrupted glucose homeostasis due to loss or dysfunction of insulin-producing beta cells. In this work, we characterize pancreatic islet development and function in zebrafish mutant for pdx1, a gene which in humans is linked to genetic forms of diabetes and is associated with increased susceptibility to Type 2 diabetes. Pdx1 mutant zebrafish have the key diabetic features of reduced beta cells, decreased insulin and elevated glucose.

In vivo three dimensional dual wavelength photoacoustic tomography imaging of the far red fluorescent protein E2-Crimson expressed in adult zebrafish.

For the first time the far red fluorescent protein (FP) E2-Crimson genetically expressed in the exocrine pancreas of adult zebrafish has been non-invasively mapped in 3D in vivo using photoacoustic tomography (PAT). The distribution of E2-Crimson in the exocrine pancreas acquired by PAT was confirmed using epifluorescence imaging and histology, with optical coherence tomography (OCT) providing complementary structural information. This work demonstrates the depth advantage of PAT to resolve FP in an animal model and establishes the value of E2-Crimson for PAT studies of transgenic models, laying the foundation for future longitudinal studies of the zebrafish as a model of diseases affecting inner organs.

Simultaneous three-dimensional photoacoustic and laser-ultrasound tomography.

A tomographic setup that provides the co-registration of photoacoustic (PA) and ultrasound (US) images is presented. For pulse-echo US-tomography laser-induced broadband plane ultrasonic waves are produced by illuminating an optically absorbing target with a short near-infrared laser pulse. Part of the same pulse is frequency doubled and used for the generation of PA waves within the object of interest.

Hybrid photoacoustic and ultrasound section imaging with optical ultrasound detection.

A setup is proposed that provides perfectly co-registered photoacoustic (PA) and ultrasound (US) section images. Photoacoustic and ultrasound backscatter signals are generated by laser pulses coming from the same laser system, the latter by absorption of some of the laser energy on an optically absorbing target near the imaged object. By measuring both signals with the same optical detector, which is focused into the selected section by use of a cylindrical acoustic mirror, the information for both images is acquired simultaneously.