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Abstract
PURPOSE: 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.