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S.M. Wren, L. Mutapcic, D.A. Leske, M.P. Fautsch, J.M. Holmes; The Effect of L–Thyroxine Supplementation in a Neonatal Rat Model of ROP . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4107.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: There is increasing evidence that hypothyroidism is a risk factor for the development of preretinal neovascularization (NV) in animal models and in infants at risk for retinopathy of prematurity (ROP). Systemic supplementation of L–Thyroxine (T4) in premature infants to correct neonatal hypothyroxinaemia and enhance neurological and respiratory development remains controversial. We hypothesized that T4 supplementation early in postnatal development, in a rat model of ROP, would decrease the incidence and severity of preretinal NV. Methods: 300 Sprague Dawley rats raised in expanded litters (n=25) were exposed to seven 24–hour cycles of 80% to 10% oxygen in constant 10% carbon dioxide from day 1 of life, followed by five days recovery in room air (hypercarbic oxygen–induced retinopathy [OIR] model of ROP). In addition, rats received a daily intraperitoneal injection of either saline (n=100), 0.05 µg/g of T4 for 3 days (n=100), 0.5 µg/g of T4 for 3 days (n=100). Rats were sacrificed on day 13 of life and retinae were assessed in a masked manner for the presence of NV, vascular area and vascular density. Results: There was no difference in the incidence of NV between the control and groups given T4 for 3 days (Saline =50%, 0.05 µg/g T4 =55%, 0.5 µg/g T4 =44%, X2, p=0.48) or in the severity of NV measured in clock hours (Kruskal–Wallis, p = 0.62). Animals receiving the higher dose of T4 had larger retinal vascular areas than animals receiving the lower dose (0.5 µg/g T4 82% ± 10% and 0.05 µg/g T4 75% ± 14%, p=0.02) and this was associated with greater weight gain (0.5 µg/g T4 = 17.7g ± 4.0g, 0.05 µg/g T4= 15.6g ± 2.9g, Saline = 15.4g ± 2.6g, p<0.0001). Conclusions: Despite the improved growth of neonatal animals supplemented with T4 in our study and the evidence that hypothyroidism may be a risk factor for ROP, there was no benefit in early T4 supplementation on the incidence or severity of NV in a hypercarbic OIR rat model of ROP. Further studies are needed using alternative doses to support this conclusion. Systemic T4 supplementation of neonates remains controversial.
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