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Updated: Mar 29, 2026
Monitoring Dynamic Growth of Retinal Vessels in Oxygen-Induced Retinopathy Mouse Model
Published on: April 2, 2021
Estrogen therapy to treat retinopathy in newborn mice
Wenjing Shi1, L I Zhu1, Yuhuan Wang1
1Department of Neonatology, Children's Hospital of Fudan University, Shanghai 201102, P.R. China.
Insights
Estrogen (E2) treatment improved retinopathy of prematurity symptoms in neonatal mice by reducing neovascularization. This suggests E2 plays a key role in ROP pathogenesis, offering potential new treatments.
Area of Science:
- Ophthalmology
- Neonatology
- Endocrinology
Background:
- Retinopathy of prematurity (ROP) is a leading cause of blindness in premature infants.
- The pathogenesis of ROP involves complex vascular changes in the developing retina.
- Estrogen (E2) is a hormone with known roles in development and vascularization.
Purpose of the Study:
- To investigate the therapeutic potential of estrogen (E2) in treating retinopathy of prematurity (ROP).
- To elucidate the role of E2 in the pathogenesis of ROP.
- To evaluate the effect of different E2 doses and administration timings on ROP development.
Main Methods:
- A mouse model of ROP was established using C57BL/6J mice exposed to hyperoxia.
- Mice were treated with varying doses of E2 or normal saline (NS) at different time points.
- Retinal vascular development, neovascularization, and endothelial cell proliferation were assessed using flat-mounts and retinal slices.
Main Results:
- E2 treatment significantly reduced neovascularization and vascular obstruction in the hyperoxia-exposed groups compared to NS controls.
- The number of endothelial cell nuclei, indicative of neovascularization, decreased significantly with E2 administration (P<0.0001).
- Optimal therapeutic effects were observed when E2 was administered during postnatal days 7-16 (P<0.05).
Conclusions:
- Estrogen (E2) treatment demonstrates a therapeutic effect on retinopathy of prematurity in a neonatal mouse model.
- E2 plays a significant role in the early stages of ROP pathogenesis.
- These findings suggest E2 as a potential pharmacological agent for preventing and treating ROP.
Abstract:
The aim of the present study was to treat retinopathy of prematurity (ROP) with estrogen (E2) so as to elucidate the role of E2 in the pathogenesis of ROP. A total of 120 postnatal 7-day-old (P7) C57BL/6J mice were selected and raised in a high-oxygen environment (75% oxygen) for 5 days, followed by 5 days in normal room air. Different doses of E2 or normal saline (NS) were injected intraperitoneally during different time-periods, and the mice were divided into 14 groups according dose of E2 injection (0.5-1.5 µg/0.05 ml) and dosing time. Blood vessel changes and hyperplasia were evaluated in flat-mounted retina and retinal slices. All mice that were exposed to room air, whether they were administered E2 or NS, showed good vascular development in the flat-mounted retina at P17. No increase in the number of endothelial cell nuclei in the new blood vessels was observed. In ascending order of E2 dose the numbers of cell nuclei were as follows: 0.18±0.129, 0.28±0.086 and 0.55±0.110. The number in the NS group was 2.12±0.373. When the results of the room-air groups were compared with those of the hyperoxia groups, a highly significant difference was found in each comparison (P<0.0001). All mice showed varying degrees of neovascularization and vascular obstruction in the flat-mounted retina at P17, and it was difficult to compare the blood vessels morphologically among these groups. The number of endothelial cell nuclei decreased following E2 injection, and the difference from the NS group exposed to hyperoxia was highly significant (P<0.0001). For all dose levels, the number of cell nuclei was the lowest when the drug was administered during P7-16, and the difference from the other two time-periods was statistically significant (P<0.05). When E2 was administered during P7-16, the number of cell nuclei was 15.5±1.993 in the 0.5-µg group, 14.23±2.49 in the 1.0-µg group and 18.05±1.62 in the 1.5-µg group. No significant difference was found among these three groups (P>0.05). In conclusion, E2 treatment during the development of retinopathy can improve symptoms in neonatal mice, suggesting that E2 plays an important role at the two initial stages in the pathogenesis of ROP. This may indicate new pharmacological measures to prevent and treat ROP.
