Long-term retinal vascular abnormalities in an animal model of retinopathy of prematurity.
OBJECTIVE
A conventional criticism of animal models of retinopathy of prematurity (ROP) concerns the common occurrence of rapid spontaneous resolution of retinal vascular sequelae. The purpose of this study was to determine whether animals subjected to a novel variable oxygen exposure protocol would undergo the rapid spontaneous resolution of retinal vascular pathology that is typical of past models.


METHODS
Newborn rats were exposed to an oxygen environment that alternated between 50% and 10% every 24 h for 14 days and then removed to room air, or were raised from birth in room air as controls. To determine early retinal vascular growth rate, both exposed and non-exposed rats were sacrificed between 3 and 28 days of age, after which eyes were enucleated and retinas dissected and stained for adenosine diphosphatase (ADPase) activity to demonstrate the vasculature. Rats were maintained in room air for 2 to 18 weeks after the variable oxygen exposure period for assessment of long-term retinal vascular abnormalities by ADPase histochemistry.


RESULTS
The retinal vasculature of oxygen-exposed rats was significantly different from that of room air-raised rats with respect to capillary density, branching frequency, and bifurcation angle. These differences were restricted to the area that was vascularized after removal to room air (the peripheral-most 25% of the retinal area), and they persisted for the duration of the study.


CONCLUSIONS
We have developed a rat model of ROP using an exposure protocol designed to create systemic oxygen levels that approximate those of premature infants. This model does not demonstrate the complete resolution of vessel abnormalities that historically has limited animal models of ROP.
Roberto
K A
KA
Arkansas Center for Eye Research, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
Tolman
B L
BL
Penn
J S
JS
D000818:Animals; D000831:Animals, Newborn; D001081:Apyrase; D002196:Capillaries / Q000473:pathology; D004195:Disease Models, Animal; D006651:Histocytochemistry; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007231:Infant, Newborn; D010100:Oxygen / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D012171:Retinal Vessels / Q000473:pathology*; D012178:Retinopathy of Prematurity / Q000473:pathology*
D001081:Apyrase; D010100:Oxygen