title: Estrogen therapy to treat retinopathy in newborn mice.
abstract: The aim of the present study was to treat retinopathy of prematurity (ROP) with estrogen (E2) so as to elucidate the role of E2in 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 E2or normal saline (NS) were injected intraperitoneally during different time-periods, and the mice were divided into 14 groups according dose of E2injection (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 E2or 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 E2dose 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 E2injection, 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 E2was 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, E2treatment during the development of retinopathy can improve symptoms in neonatal mice, suggesting that E2plays an important role at the two initial stages in the pathogenesis of ROP. This may indicate new pharmacological measures to prevent and treat ROP.
authors.affiliation: Department of Neonatology, Children's Hospital of Fudan University, Shanghai 201102, P.R. China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Neonatology, Children's Hospital of Fudan University, Shanghai 201102, P.R. China.
authors.forename: L I
authors.initials: LI
authors.lastname: Zhu
authors.affiliation: Department of Neonatology, Children's Hospital of Fudan University, Shanghai 201102, P.R. China.
authors.forename: Yuhuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Baoyang
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Honglei
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Guoming
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Department of Neonatology, Children's Hospital of Fudan University, Shanghai 201102, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
keywords: estrogen; neovascularization; retinopathy of prematurity