Cunningham S, McColm J R, Wade J, Sedowofia K, McIntosh N, Fleck B
Child Life and Health, Reproductive and Developmental Sciences, University of Edinburgh. Princess Alexandra Eye Pavilion, Edinburgh, Scotland, United Kingdom.
Invest Ophthalmol Vis Sci. 2000 Dec;41(13):4275-80.
To examine changes in the retinal vasculature of rat pups after 14 days of minute-by-minute small variations in oxygen.
Arterial oxygen data from a preterm infant who developed severe retinopathy of prematurity (ROP) was translated to equivalent values for the rat. Newborn rat pups were raised for 14 days in a cage in which a computer controlled the atmosphere to mimic the fluctuating oxygen profile (group V). Positive controls (P) of 12-hour cycles of 80% and 21% were run concurrently, as were room air controls (C). All were killed at day 14.
Groups V and P had significantly larger avascular retinal areas than C [median, interquartile range (IQR) 1.7%, 0-7.9%; 10%, 8.1-13%; 0%, 0-0%, respectively; each group n = 30]. Group P had a higher capillary branch count than C (median, IQR: 310/mm(2); 253-311 mm(2); versus 277/mm(2), 272-364/mm(2), respectively), but this was not significant using a multilevel analysis. Group V had significantly reduced capillary counts compared with C (median, 261/mm(2); IQR, 215-290/mm(2); P < 0.05 multilevel analysis). No neovascularization was seen in any group, though abnormal terminal vessels were seen at the avascular/vascular retina interface in 73% of rats in group P and 21% of rats in group V. In situ hybridization on serial sections demonstrated VEGF in the inner nuclear layer of the retina in P and V, whereas C showed trace levels only.
The vaso-obliterative stage of ROP can be induced in rats using clinically relevant oxygen levels.
研究大鼠幼崽在经历14天每分钟微小氧含量变化后视网膜血管系统的变化。
将一名发生严重早产儿视网膜病变（ROP）的早产儿的动脉氧数据换算为大鼠的等效值。新生大鼠幼崽在一个笼子里饲养14天，笼子里由计算机控制大气环境以模拟波动的氧分布情况（V组）。同时设置80%和21%的12小时循环的阳性对照组（P组）以及室内空气对照组（C组）。所有组在第14天处死。
V组和P组的无血管视网膜面积显著大于C组[中位数，四分位间距（IQR）分别为1.7%，0 - 7.9%；10%，8.1 - 13%；0%，0 - 0%，每组n = 30]。P组的毛细血管分支计数高于C组（中位数，IQR：310/mm²；253 - 311/mm²；分别对比277/mm²，272 - 364/mm²），但经多水平分析此差异无统计学意义。与C组相比，V组的毛细血管计数显著减少（中位数，261/mm²；IQR，215 - 290/mm²；多水平分析P < 0.05）。所有组均未观察到新生血管形成，不过在P组73%的大鼠和V组21%的大鼠中，在无血管/血管视网膜界面可见异常终末血管。连续切片的原位杂交显示，P组和V组视网膜内核层有血管内皮生长因子（VEGF），而C组仅显示微量水平。
使用临床相关的氧水平可在大鼠中诱导出ROP的血管闭塞期。
