Vasoproliferation in the neonatal dog model of oxygen-induced retinopathy.
OBJECTIVE
To examine the time course and relative degree of proliferative response associated with revascularization after hyperoxic insult in the dog model of oxygen-induced retinopathy.


METHODS
Mitotic cell profiles (MCPs) were counted in serial cross-sections of ADPase flat-embedded retinas of air-reared control 8-, 15-, and 22-day-old dogs and of age-matched oxygen treated animals (4 days, 100% oxygen) after return to normoxia. Sectioning and analysis were performed along the radial axis of the forming primary vasculature from optic nerve head to periphery.


RESULTS
In air-reared control animals, lumenal-associated cell mitosis was low, with an average of 9.6 MCPs/mm2 of nerve fiber layer tissue in the 8-day-old dogs, 6.5 MCPs/mm2 in the 15-day-old dogs, and 8.4 MCPs/mm2 in the 22-day-old dogs. In oxygen-treated animals, however, the number of lumenal-associated MCPs was significantly higher, with an average of 52.5 MCPs/mm2 of tissue in the 8-day-old dogs, 45.1 MCPs/mm2 in the 15-day-old dogs, and 26.8 MCPs/mm2 in the 22-day-old dogs. Additionally, extracellular spaces in avascular retina were obliterated in oxygen-treated animals.


CONCLUSIONS
This study demonstrates that in the neonatal dog, revascularization after hyperoxic insult involves a period of marked vasoproliferation that peaks somewhere between 3 to 10 days after return to room air. Oxygen-induced changes in the extravascular milieu are likely to affect the pattern of reforming vasculature and may restrict growth anteriorly.
McLeod
D S
DS
Wilmer Ophthalmological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9115, USA.
Crone
S N
SN
Lutty
G A
GA
D000375:Aging / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000473:pathology; D004195:Disease Models, Animal; D004285:Dogs; D006801:Humans; D000860:Hypoxia / Q000150:complications; D007231:Infant, Newborn; D008938:Mitosis; D008940:Mitotic Index; D009412:Nerve Fibers / Q000473:pathology; D009900:Optic Nerve / Q000473:pathology; D010100:Oxygen / Q000009:adverse effects*; D015861:Retinal Neovascularization / Q000473:pathology*; D012171:Retinal Vessels / Q000473:pathology*; D012178:Retinopathy of Prematurity / Q000209:etiology / Q000473:pathology*; D013997:Time Factors
D010100:Oxygen