Retinal region-dependent susceptibility of capillaries to high-concentration oxygen exposure and vascular endothelial growth factor receptor inhibition in neonatal mice
Retinal region-dependent susceptibility of capillaries to high-concentration oxygen exposure and vascular endothelial growth factor receptor inhibition in neonatal mice
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DOI：
10.1016/j.jphs.2015.08.010
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发表时间：
2015-10-01
影响因子：
3.5
通讯作者：
Ishii, Kunio
中科院分区：
文献类型：
--
作者：
Iizuka, Naoto;Nakahara, Tsutomu;Ishii, Kunio
由于毛细血管损失导致的视网膜血流量不足导致视网膜缺氧，导致血管生成异常，与缺血性视网膜病变有关。为了更好地了解视网膜毛细血管退化的机制和过程，我们研究了高氧和血管内皮生长因子受体（VEGFR）抑制剂诱导新生小鼠视网膜毛细血管退化的过程。我们还研究了Ca2+通道阻滞剂氨氯地平和尼卡地平对高氧诱导的毛细血管消退的影响。小鼠在出生后第7天暴露于80%氧气环境后，动脉旁毛细血管立即开始退化。氧暴露开始后24小时内建立了明显的无血管区，而视网膜血管前沿的毛细血管不受影响。阿西替尼，VEGFR酪氨酸激酶抑制剂，诱导毛细血管消退遍及视网膜血管。高浓度氧暴露对视网膜循环动脉侧毛细血管的影响比阿西替尼更优先。Ca2+通道阻滞剂显著延迟高氧诱导的毛细血管退化和动脉侧毛细血管的变化。这些结果表明，动脉收缩引起的血流量减少有助于高氧诱导的毛细血管消退。改善视网膜血流的化合物可能通过防止毛细血管损失来防止缺血。(C) 2015年作者。由Elsevier B.V.代表日本药理学会制作和主办。
Retinal blood flow insufficiency due to capillary loss induces hypoxia in the retina, leading to an abnormal angiogenesis, relating to ischemic retinopathy. To better understand the mechanism and process of retinal capillary regression, we examined the process of hyperoxia- and vascular endothelial growth factor receptor ( VEGFR) inhibitor-induced retinal capillary regression in neonatal mice. We also investigated the effects of Ca2+ channel blockers, amlodipine and nicardipine, on hyperoxia-induced capillary regression. The regression of capillaries adjacent to arteries began immediately after the mice were exposed to 80% oxygen on postnatal day 7. An apparent avascular zone was established within 24 h after the initiation of oxygen exposure, whereas capillaries in the retinal vascular front were not affected. Axitinib, an inhibitor of VEGFR tyrosine kinase, induced capillary regression throughout the retinal vasculature. High-concentration oxygen exposure affected the capillaries on the arterial side of the retinal circulation more preferentially than axitinib. The Ca2+ channel blockers significantly delayed hyperoxia-induced capillary regression and changes in the capillaries on the arterial side. These results suggest that the decreased blood flow due to arterial constriction contributes to hyperoxia-induced capillary regression. Compounds that improve the retinal blood flow may prevent ischemia by preventing capillary loss. (C) 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.