Estrogen therapy to treat retinopathy in newborn mice.

The aim of the present study was to treat retinopathy of prematurity (ROP) with estrogen (E-2) so as to elucidate the role of E-2 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 E-2 or normal saline (NS) were injected intraperitoneally during different time-periods, and the mice were divided into 14 groups according dose of E-2 injection (0.5-1.5 mu g/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 E-2 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 E-2 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 E-2 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 E-2 was administered during P7-16, the number of cell nuclei was 15.5 +/- 1.993 in the 0.5-mu g group, 14.23 +/- 2.49 in the 1.0-mu g group and 18.05 +/- 1.62 in the 1.5-mu g group. No significant difference was found among these three groups (P>0.05). In conclusion, E-2 treatment during the development of retinopathy can improve symptoms in neonatal mice, suggesting that E-2 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.