Oshima Yuji, Deering Tye, Oshima Sachiko, Nambu Hiroyuki, Reddy P Seshidhar, Kaleko Michael, Connelly Sheila, Hackett Sean F, Campochiaro Peter A
Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
J Cell Physiol. 2004 Jun;199(3):412-7. doi: 10.1002/jcp.10442.
Increased expression of vascular endothelial growth factor (VEGF) in the retina starting after postnatal day (P)7 results in neovascularization originating from deep retinal capillaries, but not those in the superficial capillary bed. Doxycycline was administered starting P0 to double transgenic mice with inducible expression of VEGF in the retina. These mice showed proliferation and dilation of superficial retinal capillaries, indicating that at this stage of development, the superficial capillaries are sensitive to the effects of VEGF. Angiopoietin-2 (Ang2) is expressed along the surface of the retina for several days after birth, but by P7 and later, Ang2 is only expressed in the region of the deep capillary bed. In mice with ubiquitous doxycycline-inducible expression of Ang2, in the absence of doxycycline, intravitreous injection of a gutless adenoviral vector expressing VEGF (AGV.VEGF) resulted in neovascularization of the cornea and iris, but no retinal neovascularization. After treatment with doxycycline to induce Ang2 expression, intravitreous injection of AGV.VEGF caused retinal neovascularization in addition to corneal and iris neovascularization. The retinal neovascularization originated from both the superficial and deep capillary beds. These data suggest that Ang2 promotes sensitivity to the angiogenic effects of VEGF in retinal vessels.
出生后第7天（P7）开始，视网膜中血管内皮生长因子（VEGF）表达增加会导致源自视网膜深层毛细血管而非浅层毛细血管床的新生血管形成。从出生后第0天（P0）开始对视网膜中VEGF可诱导表达的双转基因小鼠给予强力霉素。这些小鼠表现出视网膜浅层毛细血管的增殖和扩张，表明在这个发育阶段，浅层毛细血管对VEGF的作用敏感。血管生成素-2（Ang2）在出生后几天沿视网膜表面表达，但到P7及以后，Ang2仅在深层毛细血管床区域表达。在Ang2可通过强力霉素普遍诱导表达的小鼠中，在未使用强力霉素的情况下，玻璃体内注射表达VEGF的无内脏腺病毒载体（AGV.VEGF）会导致角膜和虹膜新生血管形成，但不会导致视网膜新生血管形成。在用强力霉素诱导Ang2表达后，玻璃体内注射AGV.VEGF除了导致角膜和虹膜新生血管形成外，还会导致视网膜新生血管形成。视网膜新生血管形成源自浅层和深层毛细血管床。这些数据表明，Ang2可提高视网膜血管对VEGF血管生成作用的敏感性。
