PUBLICATION
Activation of retinal angiogenesis in hyperglycemic pdx1-/- zebrafish mutants
- Authors
- Wiggenhauser, L.M., Qi, H., Stoll, S.J., Metzger, L., Bennewitz, K., Poschet, G., Krenning, G., Hillebrands, J.L., Hammes, H.P., Kroll, J.
- ID
- ZDB-PUB-200307-17
- Date
- 2020
- Source
- Diabetes 69(5): 1020-1031 (Journal)
- Registered Authors
- Kroll, Jens, Stoll, Sandra
- Keywords
- none
- MeSH Terms
-
- Gene Deletion
- Vascular Endothelial Growth Factor A/metabolism
- Gene Expression Regulation/drug effects
- Nitric Oxide/metabolism
- Homeodomain Proteins/genetics
- Homeodomain Proteins/metabolism*
- Animals
- Blood Glucose
- CRISPR-Cas Systems
- Hyperglycemia*
- Larva
- Retinal Neovascularization
- Trans-Activators/genetics
- Trans-Activators/metabolism*
- Protein Kinase Inhibitors/pharmacology
- Neovascularization, Pathologic*
- Zebrafish
- Phthalazines/pharmacology
- Pyridines/pharmacology
- Retinal Vessels/physiology*
- PubMed
- 32139597 Full text @ Diabetes
Citation
Wiggenhauser, L.M., Qi, H., Stoll, S.J., Metzger, L., Bennewitz, K., Poschet, G., Krenning, G., Hillebrands, J.L., Hammes, H.P., Kroll, J. (2020) Activation of retinal angiogenesis in hyperglycemic pdx1-/- zebrafish mutants. Diabetes. 69(5):1020-1031.
Abstract
Progression from the initial vascular response upon hyperglycemia to a proliferative stage with neovacularizations is the hallmark of proliferative diabetic retinopathy. Here we report on the novel diabetic pdx1-/- zebrafish mutant as model for diabetic retinopathy that lacks the transcription factor pdx1 via CRISPR/Cas9-mediated gene knockout leading to disturbed pancreatic development and hyperglycemia. Larval pdx1-/- mutants prominently show vasodilation of blood vessels via increased vascular thickness in the hyaloid network as direct developmental precursor of the adult retinal vasculature in zebrafish. In adult pdx1-/- mutants, impaired glucose homeostasis induces increased hyperbranching and hypersprouting with new vessel formation in the retina and aggravation of the vascular alterations from the larval to the adult stage. Both vascular aspects respond to antiangiogenic and antihyperglycemic pharmacological interventions in the larval stage and are accompanied by alterations in the nitric oxide metabolism. Thus, the pdx1-/- mutant represents a novel model to study mechanisms of hyperglycemia-induced retinopathy wherein extensive proangiogenic alterations in blood vessel morphology and metabolic alterations underlie the vascular phenotype.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping