Extraretinal neovascularization induced by hypoxic episodes in the neonatal rat.
Extraretinal neovascularization induced by hypoxic episodes in the neonatal rat.
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DOI：
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发表时间：
1994-07
影响因子：
4.4
通讯作者：
Xavier Reynaud;C. Dorey
中科院分区：
文献类型：
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作者：
Xavier Reynaud;C. Dorey
目的验证缺氧诱导视网膜新生血管形成的假说。方法将新生大鼠暴露于80%氧气中，每天在室内空气中短时间间断，持续11天，使无血管视网膜产生相对缺氧。在室内空气中持续1/2小时或1小时后突然复氧，或1/2小时后逐渐复氧至80%氧持续3小时，以延长缺氧时间。在11天的间断氧气暴露结束时，将动物留在室内空气中6天。结果新生血管的发生率与缺氧时间呈剂量-反应关系。约3小时的时间在94%的动物中产生新血管形成（至少一只眼睛）。暴露于长时间缺氧的动物的外周无血管视网膜的总面积大于暴露于短时间缺氧的动物。新生血管的发生率与周围无血管视网膜的总面积密切相关，78%的病例发生在下象限。在一些视网膜中观察到3期早产儿视网膜病变（ROP）的其他特征，包括动静脉分流和脊。结论缺氧可诱导大鼠视网膜外新生血管形成，短暂缺氧可加重ROP的进展。由于新生血管的高发生率和定位的可预测性，该模型可用于血管生成的研究和抗血管生成或抗氧化物质的评价。
PURPOSE To test the hypothesis that hypoxia induces retinal neovascularization. METHODS To produce relative hypoxia in the avascular retina, newborn rats were exposed for 11 days to 80% oxygen interrupted daily by short episodes in room air. Episodes in room air lasted 1/2 hour or 1 hour followed by abrupt reintroduction, or 1/2 hour followed by progressive reintroduction to 80% oxygen lasting 3 hours to prolong the period of hypoxia. At the end of the 11 days of interrupted oxygen exposure, the animals were left in room air for 6 days. RESULTS The incidence of neovascularization exhibited a dose-response relationship to the period out of 80% oxygen. Periods of approximately 3 hours produced neovascularization (in at least one eye) in 94% of the animals. The total area of the peripheral avascular retina was larger in animals exposed to prolonged periods of hypoxia than in those exposed for shorter periods. The incidence of neovascularization was strongly associated with the total area of the peripheral avascular retina and occurred in the inferior quadrant in 78% of the cases. Additional features of stage 3 retinopathy of prematurity (ROP), including arteriovenous shunts and ridges, were observed in some retinas. CONCLUSIONS These data demonstrate that hypoxic episodes can induce extraretinal neovascularization in the rat and suggest that brief periods of oxygen deficiency could exacerbate progression of ROP. With the high incidence and predictability of localization of neovascularization, this model could be useful for the study of angiogenesis and for evaluation of antiangiogenic or antioxidant substances.