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M. Mookadam, D.A. Leske, B.N. I. Floyd, M.P. Fautsch, J.M. Holmes; MMI–Induced Retinal Neovascularization Analogous to ROP in Neonatal Rats . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4042.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To determine the effect of methimazole (MMI), an anti–thyroid drug known to reduce serum levels of IGF–1, on normal neonatal retinal vasculature, and on the incidence and severity of neovascularization (NV) in an acidosis–induced retinopathy (AIR) model of retinopathy of prematurity (ROP). Methods: 300 Sprague–Dawley rats were raised in expanded litters of 25 in room air and exposed to (a) 10 days of MMI (given as a 0.1% solution to nursing mothers) from day 1 of life (n=50), (b) acidosis alone via NH4Cl gavage, 20mmol/kg bodyweight, twice daily, from days 2 to 7 (our established AIR model) (n= 100), and (c) 10 days of MMI in the AIR model (n=100). An additional 2 litters (n=50) served as controls. All rats were sacrificed on day 10 of life. Left eyes were fixed and retinas were dissected and ADPase stained. Flatmounted retinas were graded for presence and severity of NV in a masked manner. In a parallel study to determine serum IGF–1 levels, an additional 100 rats were raised in expanded litters of 25 and exposed to identical treatments as described above (i.e. MMI alone (n=25), AIR alone (n=25), MMI plus AIR (n=25), and control (n=25)). Blood samples were obtained via carotid artery cut–down on day 10 and serum IGF–1 levels were measured by radioimmunoassay. Results:NV occurred in 31% of MMI alone rats, 24% of AIR alone, 33% of MMI plus AIR rats and 0% of controls. There were no significant differences in severity of NV between groups. Compared to controls (214 ng/ml ± 43), serum IGF–1 levels were reduced in MMI alone (136 ng/ml ± 17, P= 0.001) and MMI plus AIR rats (158 ng/ml ± 17, P= 0.008). Serum IGF–1 levels were similar in controls and AIR rats (201 ng/ml ± 60, P=0.98). Conclusions: The anti–thyroid drug MMI induces NV in neonatal rats despite low levels of IGF–1. The effect of acidosis and MMI were not additive. Supranormal levels of serum IGF–1 are not necessary for induction of NV in neonatal retinas. Further studies are warranted on the roles of serum IGF–1 and thyroid hormones in the pathogenesis of ROP.
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