PUBLICATION
The Inhibitory Effect of Selected D2 Dopaminergic Receptor Agonists on VEGF-Dependent Neovascularization in Zebrafish Larvae: Potential New Therapy in Ophthalmic Diseases
- Authors
- Kasica, N., Święch, A., Saładziak, K., Mackiewicz, J., Osęka, M.
- ID
- ZDB-PUB-220413-5
- Date
- 2022
- Source
- Cells 11(7): (Journal)
- Registered Authors
- Keywords
- D2 dopaminergic receptor agonist, angiogenesis, bromocriptine, cabergoline, hyaloid-retinal vessels (HRVs), intersegmental vessels (ISVs), pergolide, vascular endothelial growth factor, zebrafish
- MeSH Terms
-
- Angiogenesis Inhibitors/pharmacology
- Angiogenesis Inhibitors/therapeutic use
- Animals
- Bevacizumab
- Bromocriptine/metabolism
- Bromocriptine/pharmacology
- Cabergoline/metabolism
- Dopamine Agonists*/metabolism
- Dopamine Agonists*/pharmacology
- Dopamine Agonists*/therapeutic use
- Hypoxia/pathology
- Larva/metabolism
- Neovascularization, Pathologic/metabolism
- Pergolide/metabolism
- Pergolide/pharmacology
- Vascular Endothelial Growth Factor A/metabolism
- Zebrafish*/metabolism
- PubMed
- 35406766 Full text @ Cells
Citation
Kasica, N., Święch, A., Saładziak, K., Mackiewicz, J., Osęka, M. (2022) The Inhibitory Effect of Selected D2 Dopaminergic Receptor Agonists on VEGF-Dependent Neovascularization in Zebrafish Larvae: Potential New Therapy in Ophthalmic Diseases. Cells. 11(7):.
Abstract
Pathological angiogenesis is correlated with many ophthalmic diseases. The most common are exudative age-related macular degeneration and proliferative diabetic retinopathy. The current treatment for these diseases is based on regularly administered anti-VEGF antibodies injections. In the study, we investigated selected D2 dopaminergic receptor agonists, namely bromocriptine, cabergoline and pergolide, on hypoxia-induced neovascularization. We used the zebrafish laboratory model, specifically three-day post fertilization (dpf) Tg(fli-1: EGFP) zebrafish larvae. To induce abnormal angiogenesis of hyaloid-retinal vessels (HRVs) and intersegmental vessels (ISVs), the larvae were treated with cobalt chloride (II) (CoCl2) (a hypoxia-inducing agent) from 24 h post fertilization. The inhibitory role of D2 dopaminergic receptor agonists was investigated using confocal microscopy and qPCR. Additionally, the results were compared to those obtained in the group treated with CoCl2 followed by bevacizumab, the well-known antiangiogenic agent. Confocal microscopy analyses revealed severe deformation of vessels in the CoCl2 treated group, while co-incubation with bromocriptine, cabergoline, pergolide and bevacizumab, respectively, significantly inhibited abnormalities of angiogenesis. The qPCR analyses supported the protective role of the chosen dopaminergic agonists by demonstrating their influence on CoCl2-derived upregulation of vegfaa expression. The present results suggest that the D2 receptor agonists can be considered as a new direction in research for antiangiogenic therapy.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping