Abstract
Purpose: :
Retinal neovascularization (RNV) is an important pathological event and a major cause of blindness. Vascular inflammation and oxidative stress have been shown to play a role in the induction and progression of RNV. We characterized the effects of the flavonoid trans-chalcone in preventing RNV in a model of ischemic retinopathy. Trans-chalcone-derived flavonoids have been previously shown to be negative modulators of inflammatory responses as well as tumor angiogenesis.
Methods: :
Ischemic retinopathy was induced in neonatal mice following the protocol of the mouse model of oxygen-induced retinopathy (Smith, LEH. et al. 1994). Trans-chalcone was administered intra-peritoneum at the dose of 25mg/Kg/day. Vascular density was assessed by morphometric analysis of flat mounted retinas stained with Texas red-Isolectin B4. Western blotting and immnuno-histochemical analyses were conducted to determine the levels of VEGF, ICAM-1 and the transcriptional activators STAT3 (tyrosine-phosphorylated) and NF-kB (phosphorylated p65).
Results: :
Treatment with trans-chalcone significantly inhibited RNV in the ischemic retina, as shown by decreased number of neovascular tufts. Trans-chalcone also blocked ischemia-induced VEGF and ICAM-1 expression and this effect correlated with trans-chalcone-mediated inhibition of activated STAT3 and NF-kB.
Conclusions: :
Our results show that trans-chalcone effectively prevents RNV in the murine retina thus suggesting that chalcone-derived flavonoids may be beneficial in preventing pathological neovascularization in the ischemic retina.
Keywords: antioxidants • inflammation • ischemia