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L. Mutapcic, S.M. Wren, D.A. Leske, M.P. Fautsch, J.M. Holmes; The Effect of L–Thyroxine Supplementation on Retinal Vascular Development in Neonatal Rats . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4106.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Hypothyroidism has been suggested as a risk factor for retinopathy of prematurity (ROP). L–Thyroxine (T4) supplementation in premature infants is controversial, but has been associated with accelerated neuroretinal development in neonatal animals. The neonatal rat retina is incompletely vascularized at birth, providing a model for the human premature infant retina. We hypothesized that T4 supplementation would accelerate vascular development of normal neonatal rat retina. Methods: 220 Sprague Dawley rats were raised in litters of 10 in room air and received either 0.05 µg/g, 0.5 µg/g, or 1.0 µg/g of intraperitoneal T4 or saline control beginning on day 1 of life for 3 days, 7 days, or 3 days followed by 4 days recovery. Rats were sacrificed on either day 4 or day 8 of life. Left eyes were fixed, retinae dissected and ADPase–stained. Flatmounted retinae were digitized and total retinal areas and retinal vascular density were evaluated in a masked manner. Serum TSH was also measured in each group at each time point. Results: Vascularized retinal area was reduced in animals receiving 1 µg/g T4 for 3 days followed by 4 days recovery compared to saline controls (85 ± 6% vs. 92 ± 3%, p=0.002). Retinal vascular density was also reduced in animals receiving daily 1 µg/g T4 compared to saline controls at both day 4 (16.8 ± 1.4 vessels/mm vs. 18.3 ± 1.3 vessels/mm, p=0.04) and day 8 (14.4 ± 1.3 vessels/mm vs. 16.8 ± 1.1 vessels/mm, p=0.0006). However, retinal vascular density returned to normal, following 4 days of recovery. At lower doses of T4 (0.05 µg/g and 0.5 µg/g for 3 or 7 days) and at 1 µg/g T4 for 7 days, there was no effect on vascularized retinal area. Serum TSH was suppressed in all T4 groups following 7 days of treatment and 3 days of treatment followed by recovery. Conclusions: Systemic T4 supplementation at 1 µg/g per day was detrimental to retinal vascular development in neonatal animals. If these effects are paralleled in human neonates, T4 supplementation might increase, rather than decrease, the risk of developing ROP. Further work on the role of T4 in the pathogenesis of ROP is warranted.
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