Sarlos Stella, Rizkalla Bishoy, Moravski Christina J, Cao Zemin, Cooper Mark E, Wilkinson-Berka Jennifer L
Department of Physiology, University of Melbourne, Parkville, Victoria, Australia.
Am J Pathol. 2003 Sep;163(3):879-87. doi: 10.1016/S0002-9440(10)63448-7.
There is evidence that angiotensin II, vascular endothelial growth factor (VEGF), angiopoietins, and their cognate receptors participate in retinal angiogenesis. We investigated whether angiotensin type 2-receptor blockade (AT2-RB) reduces retinal angiogenesis and alters the expression of VEGF/VEGF-R2 and angiopoietin-Tie2. Retinopathy of prematurity (ROP) was induced in Sprague Dawley (SD) rats by exposure to 80% oxygen from postnatal (P) days 0 to 11, followed by 7 days in room air. ROP shams were in room air from P0-18. A group of ROP rats received the AT2-RB, PD123319, by mini-osmotic pump (5 mg/kg/day) from P11-18 (angiogenesis period). Evaluation of the retinal status of the AT2 receptor indicated that this receptor, as assessed by real-time PCR, immunohistochemistry, and in vitro autoradiography, was present in the retina, was more abundant than the AT1 receptor in the neonatal retina, and was increased in the ROP model. AT2-RB reduced retinal angiogenesis. VEGF and VEGF-R2 mRNA were increased in ROP and localized to blood vessels, ganglion cells, and the inner nuclear layer, and were decreased by PD123319. Angiopoietin2 and Tie2, but not angiopoietin1 mRNA were increased with ROP, and angiopoietin2 was reduced with PD123319. This study has identified a potential retinoprotective role for AT2-RB possibly mediated via interactions with VEGF- and angiopoietin-dependent pathways.
有证据表明，血管紧张素II、血管内皮生长因子（VEGF）、血管生成素及其同源受体参与视网膜血管生成。我们研究了2型血管紧张素受体阻断（AT2-RB）是否能减少视网膜血管生成，并改变VEGF/VEGF-R2和血管生成素-Tie2的表达。通过从出生后（P）第0天至第11天暴露于80%氧气，随后在室内空气中饲养7天，诱导Sprague Dawley（SD）大鼠发生早产儿视网膜病变（ROP）。ROP假手术组从P0至18天置于室内空气中。一组ROP大鼠在P11至18天（血管生成期）通过微型渗透泵接受AT2-RB药物PD123319（5mg/kg/天）。对视网膜AT2受体状态的评估表明，通过实时PCR、免疫组织化学和体外放射自显影评估，该受体存在于视网膜中，在新生视网膜中比AT1受体更丰富，并且在ROP模型中增加。AT2-RB减少了视网膜血管生成。VEGF和VEGF-R2 mRNA在ROP中增加，并定位于血管、神经节细胞和内核层，且被PD123319降低。血管生成素2和Tie2而非血管生成素1 mRNA在ROP中增加，血管生成素2被PD123319降低。本研究确定了AT2-RB可能通过与VEGF和血管生成素依赖性途径相互作用介导的潜在视网膜保护作用。
