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Updated: Apr 18, 2026
Oxygen-Induced Retinopathy Model for Ischemic Retinal Diseases in Rodents
Published on: September 16, 2020
17β-estradiol ameliorates oxygen-induced retinopathy in the early hyperoxic phase
Hongbing Zhang1, Xiaodong Wang2, Kun Xu1
1Eye Institute of Shaanxi Province and Xi'an First Hospital, #30, Fenxiang, Nanda Avenue, Xi'an 710002, PR China.
Insights
Early treatment with 17β-estradiol (17β-E2) may prevent retinopathy of prematurity (ROP) by reducing oxidative stress and improving retinal vascularization in a preclinical model. This approach targets early hyperoxic phases before neovascularization occurs.
Area of Science:
- Ophthalmology
- Neonatology
- Developmental Biology
- Pharmacology
Background:
- Retinopathy of prematurity (ROP) is a leading cause of blindness in premature infants.
- Current treatments for ROP focus on peripheral retinal ablation, which has limitations.
- Early intervention targeting oxidative stress and vascular development is needed.
Purpose of the Study:
- To investigate retinal morphological and oxidative stress changes in early oxygen-induced retinopathy (OIR).
- To evaluate the therapeutic effect of 17β-estradiol (17β-E2) on early OIR.
- To explore the role of estrogen receptors in mediating 17β-E2's effects.
Main Methods:
- Induction of OIR in rat pups via hyperoxia.
- Assessment of retinal morphology, capillary-free areas, and oxidative stress markers (MDA, NADPH oxidase activity).
- Administration of 17β-E2 and an estrogen receptor antagonist (ICI182780) to assess treatment effects.
Main Results:
- Hyperoxia induced significant capillary-free areas and elevated oxidative stress markers (MDA, NADPH oxidase) in retinas.
- 17β-E2 treatment dose-dependently reduced capillary-free areas and oxidative stress markers.
- 17β-E2 modulated VEGF levels and its effects were reversed by ICI182780, suggesting estrogen receptor involvement.
Conclusions:
- Antioxidant treatment during the early hyperoxic phase of OIR, before neovascularization, may be more effective than late-phase treatments.
- 17β-E2 shows potential as a therapeutic agent for preventing ROP by mitigating oxidative stress and promoting healthy vascular development.
- Targeting early OIR phases with agents like 17β-E2 could offer a novel strategy to prevent ROP-related blindness.
Abstract:
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.
