The effect of L-thyroxine supplementation in a neonatal rat model of ROP.
OBJECTIVE
The role of L-thyroxine in retinopathy of prematurity (ROP) is controversial. Recent animal studies suggest both high and low levels of serum thyroxine (exogenous supplementation and pharmacologic inhibition) are associated with preretinal neovascularization (NV) or retinal vascular retardation, a precursor of NV. To address this controversy, we studied L-thyroxine supplementation in an animal model of ROP.


METHODS
Five hundred newborn Sprague-Dawley rats were raised in 20 expanded litters of 25, under conditions of fluctuating high and low oxygen and high carbon dioxide, to induce preretinal neovascularization. Rats received either 3 days of intraperitoneal T4, 7 days of T4 or saline control. Doses of T4 ranged from 0.005 microg/g to 0.5 microg/g. Retinae from left eyes were dissected, flat-mounted, and ADPase-stained. The presence and severity of NV, retinal vascular area, and retinal vascular density were scored in a masked manner.


RESULTS
The incidence of NV was similar in rats receiving either 3 days of T4 or 7 days of T4 and saline controls (55% and 43% NV in 3-day experiments [0.05 microg g-1 day-1 and 0.5 microg g-1 day-1] compared with 51% in saline controls, p = 0.49; 52% and 38% in 7-day experiments [0.005 microg g-1 day-1 and 0.05 microg g-1 day-1], p = 0.22). Retinal vascular area and vessel density were also similar to saline controls.


CONCLUSIONS
Systemic T4 supplementation does not increase, or decrease, the incidence or severity of preretinal neovascularization in an animal model of ROP, despite its positive effect on overall animal growth. Further work is needed to elucidate the potential role of premature infant hypothyroidism in the pathogenesis of ROP.
Wren
Siobhan M E
SM
Department of Ophthalmology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Leske
David A
DA
Mutapcic
Lejla
L
Fautsch
Michael P
MP
Holmes
Jonathan M
JM
D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D000831:Animals, Newborn; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D006801:Humans; D007231:Infant, Newborn; D051381:Rats; D017207:Rats, Sprague-Dawley; D015861:Retinal Neovascularization / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D012178:Retinopathy of Prematurity / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D012720:Severity of Illness Index; D013974:Thyroxine / Q000008:administration & dosage*; D016896:Treatment Outcome
D013974:Thyroxine