Retinopathy of prematurity (ROP) is a major and leading cause of
blindness in premature infants. It has been realized that early treatment for ROP is important. However, all the early treatments of ROP are focusing on peripheral
retinal ablation which does not surmount the limit of extinguishing
retinal neovascularization and protecting the retinas of children with ROP from the injury of ablation. In this study, we investigated the morphological changes of retina and oxidative stress alterations in the early phase of
oxygen-induced retinopathy (OIR) and tested the effects of 17β-estradiol (17β-E2), a nonselective
estrogen receptor (ER) agonist, on early phase OIR development. We found that large central capillary-free areas were induced in the retinas of pups exposed to
hyperoxia on postnatal day 9 (P9), whereas vascularization was almost complete in the retinas of pups exposed to normoxia at the same age. The concentrations of malondiadehyde (MDA), an end-product of oxidative stress, and
nicotinamide adenine dinucleotide phosphate (
NADPH) oxidase, a major
enzyme producing
free radicals, as well as the activity of
NADPH oxidase were significantly elevated in the retinas of pups exposed to
hyperoxia on P9 and postnatal day 13 (P13) compared to those in age matched pups exposed to normoxia. Treatment with 17β-E2 decreased not only the percentage of the central capillary-free area to total retina area but also the concentrations of MDA and
NADPH oxidase as well as the activity of
NADPH oxidase in a dose-dependent manner in pups exposed to
hyperoxia on p9 and P13. The concentration of
VEGF was significantly decreased on P9 but increased on P14 in the retinas of pups exposed to
hyperoxia, whereas it was significantly elevated on P9 but decreased on P14 in the retinas of pups treated with 17β-E2. The effect of 17β-E2 could be reversed by the co-treatment with
ICI182780, a high affinity
estrogen receptor antagonist, which suggested that 17β-E2 might exert its effect on early hyperoxic phase of OIR through
estrogen receptor. Our results suggest that treatment with
antioxidant drugs at early hyperoxic phase of ROP even before the appearance of
retinal neovascularization may be more effective than their application to ROP at late phase, which may abolish the deleterious factors that contribute to
retinal neovascularization and promote retinal blood vessels to develop healthily.