Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich.
mehr Informationen...
Activation of Retinal Angiogenesis in Hyperglycemic pdx1 -/- Zebrafish Mutants
Ist Teil von
Diabetes (New York, N.Y.), 2020-05, Vol.69 (5), p.1020-1031
Ort / Verlag
United States: American Diabetes Association
Erscheinungsjahr
2020
Link zum Volltext
Quelle
Free E-Journal (出版社公開部分のみ）
Beschreibungen/Notizen
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
zebrafish mutant as a model for diabetic retinopathy that lacks the transcription factor
through CRISPR-Cas9-mediated gene knockout leading to disturbed pancreatic development and hyperglycemia. Larval
mutants prominently show vasodilation of blood vessels through increased vascular thickness in the hyaloid network as direct developmental precursor of the adult retinal vasculature in zebrafish. In adult
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
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.