Prevention of Retinal Vaso-obliteration in Oxygen Induced Retinopathy by Flavonoids in the Newborn Rat

Xanthi Couroucli

PURPOSE: In this study, we tested the hypothesis that exposure of newborn rats to a combination of the flavonoid β-napthoflavone (BNF) and hyperoxia would alleviate vaso-obliteration and abnormal neovascularization compared to those exposed to hyperoxia alone.

METHODS: Newborn Fisher 344 rats were maintained in room air or hyperoxia (90% O2) for 7 days. Some animals were treated i.p. with BNF (20 mg/kg) or vehicle, once daily for the first 5 days of hyperoxia, and were sacrificed at selected time points. Vascular densities of flat mounted retinas were assessed. mRNA expression of VEGF, its receptors and cytochrome P4501B1 (CYP1B1) was determined by real time RT-PCR.

RESULTS: After 7 days of exposure to hyperoxia, we observed severe vaso-obliteration, compared to the hyperoxia + BNF. Seven to thirty days after termination of hyperoxia, the animals displayed abnormal retinal vessels, whereas those given BNF+ hyperoxia showed significantly lesser extent of neovascularization. At the later time points, VEGF mRNA expression in the hyperoxia group was much higher than that of the BNF+ hyperoxia group. On the other hand, the expression of VEGFR-1 and sFLT-1, but not VEGFR2, was upregulated by BNF + hyperoxia, compared to the hyperoxia only group. Interestingly, retinal CYP1B1 expression was also augmented in the BNF + hyperoxia group.

CONCLUSIONS: Our study supported the hypothesis that BNF protects retinas from oxygen-induced retinopathy, and that upregulation of VEGFR1 as well as CYP1B1 contributes to the retinoprotective effects of BNF. Further studies are needed to elucidate the mechanisms of the protective action of BNF.