The anti-thyroid drug methimazole aggravated neovascularization in the oxygen-induced retinopathy rat model of ROP

Abstract

To determine the effect of methimazole (MMI) on retinal vascular development in the oxygen-induced retinopathy neonatal rat. It was an experimental study. Control and MMI-exposed newborn rats were raised either in room air or variable oxygen (40%/15%) every 24 hours until P14. All groups were then exposed to room air between postnatal day P14 and P18. Dams drank either tap water or water containing 0.1% MMI. Eyes in all groups were fixed, and retinas were dissected and stained with adenosine diphosphatase, then analyzed for retinal vascular areas, vascular density, and NV incidence and severity. Serum IGF-1 level was measured by radioimmunoassay. Body weight were measured every day. NV incidence between groups were analyzed with Chi-square tests. Ratio of peripheral avascular area to the whole retina area, vascular density, the nucleus of vascular endothelial cells breaking inner limiting membrane count and Serum IGF-1 level between groups were tested by One-Way ANOVA analysis and independent-samples t-test. Compared with untreated 40%/15% pups, 40%/15% newborn rats receiving MMI exhibited significant changes in NV incidence (26%:57%, χ(2) = 4.38 P = 0.04) and the nucleus of vascular endothelial cells breaking inner limiting membrane count (33.17 ± 3.06:65.64 ± 3.85, t = 17.73, P = 0.00). Ratio of peripheral avascular area to the whole retina area of MMI treated 40%/15% rats was 6.37% ± 1.23%, and the development of retinal blood vessels in other groups reached periphery. Retinal NV was not found in MMI control retinas, although retinal vascular density was significantly lower (P < 0.05) in MMI-treated pups (52.57 ± 4.14) than in the control group (95.21 ± 6.17). Serum IGF-1 levels were markedly (P < 0.05) reduced in MMI treated control rats (235.94 ± 29.09) mg/L compared with untreated control animals (536.43 ± 32.65) mg/L and in MMI treated 40%/15% rats (227.24 ± 19.59) mg/L compared with untreated 40%/15% group (526.50 ± 26.83) mg/L. Compared with non-MMI pups, newborn rats receiving MMI exhibited significant growth retardation in body weight. MMI aggravates NV in oxygen-induced retinopathy neonatal rats. This may be mediated by the initial suppression of serum IGF-1. The relationship between the temporal course of serum IGF-1 and NV in immature retinas needs further investigation.