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.
Dopamina oraz agoniści receptorów dopaminergicznych D2 wykazują działanie hamujące aktywność czynnika wzrostu śródbłonka naczyniowego. Działanie to zostało udowodnione w wielu chorobach nowotworowych oraz w zespole hiperstymulacji jajników. Dotychczas przeprowadzone badania wskazują na potencjalne zastosowanie tych substancji również w leczeniu chorób oczu przebiegających ze zwiększonym uwalnianiem czynnika wzrostu śródbłonka naczyniowego, takich jak: wysiękowa postać zwyrodnienia plamki związanego z wiekiem, cukrzycowy obrzęk plamki lub proliferacyjna postać retinopatii cukrzycowej. W niniejszej pracy przedstawiono przegląd najnowszych danych literaturowych na temat potencjalnego zastosowania agonistów dopaminergicznych D2 w leczeniu chorób oczy zależnych od naczyniowo-śródbłonkowego czynnika wzrostu (VEGF).
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