Vinores S A, Youssri A I, Luna J D, Chen Y S, Bhargave S, Vinores M A, Schoenfeld C L, Peng B, Chan C C, LaRochelle W, Green W R, Campochiaro P A
The Wilmer Opthalmologic Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287-9289, USA.
Histol Histopathol. 1997 Jan;12(1):99-109.
Vascular endothelial growth factor (VEGF) is induced by hypoxia and it has been implicated in the development of iris and retinal neovascularization (NV) in ischemic retinopathies in which it has been suggested that Muller cells are responsible for increased VEGF production. VEGF, however, is also known to be a potent mediator of vascular permeability in other tissues and may perform this function in retina. Immunohistochemical staining for VEGF was performed on a variety of human and experimental ischemic and non-ischemic ocular disorders in which blood retinal barrier (BRB) breakdown is known to occur to determine if there is an upregulation of VEGF in these conditions. We found increased VEGF immunoreactivity in ganglion cells of rats with oxygen-induced ischemic retinopathy and in ganglion cells, the inner plexiform layer, and some cells in the inner nuclear layer of rats with experimental autoimmune uveoretinitis (EAU), in which there was no identifiable ischemia or NV. In rats with EAU, VEGF staining intensity increased from 8 to 11 days after immunization, coincident with BRB failure. These results were confirmed using two distinct anti-VEGF antibodies and by immunoblot and the immunohistochemical staining was eliminated by pre-incubating the antibodies with VEGF peptide. VEGF staining was also increased in the retina and iris of patients with ischemic retinopathies, such as diabetic retinopathy and retinal vascular occlusive disease, and in patients with disorders in which retinal ischemia does not play a major role, such as aphakic/ pseudophakic cystoid macular edema, retinoblastoma, ocular inflammatory disease or infection, and choroidal melanoma. VEGF was primarily localized within retinal neurons and retinal pigmented epithelial cells in these cases. In addition or in association with its role of inducing NV, VEGF may contribute to BRB breakdown in a variety of ocular disorders and blockage of VEGF signaling may help to reduce some types of macular edema.
血管内皮生长因子（VEGF）由缺氧诱导产生，并且在缺血性视网膜病变的虹膜和视网膜新生血管形成（NV）过程中发挥作用。有研究表明，在缺血性视网膜病变中，Muller细胞会导致VEGF产生增加。然而，VEGF也是其他组织中血管通透性的有效介质，可能在视网膜中发挥此功能。我们对各种已知会发生血视网膜屏障（BRB）破坏的人类和实验性缺血性及非缺血性眼部疾病进行了VEGF免疫组织化学染色，以确定在这些情况下VEGF是否上调。我们发现，在氧诱导的缺血性视网膜病变大鼠的神经节细胞中，以及在实验性自身免疫性葡萄膜视网膜炎（EAU）大鼠的神经节细胞、内网状层和内核层的一些细胞中，VEGF免疫反应性增加，而在这些大鼠中未发现明显的缺血或NV。在EAU大鼠中，VEGF染色强度在免疫后8至11天增加，与BRB破坏同时发生。使用两种不同的抗VEGF抗体、免疫印迹法证实了这些结果，并且通过将抗体与VEGF肽预孵育消除了免疫组织化学染色。在缺血性视网膜病变患者（如糖尿病性视网膜病变和视网膜血管阻塞性疾病）以及视网膜缺血不起主要作用的疾病患者（如无晶状体/假晶状体性黄斑囊样水肿、视网膜母细胞瘤、眼部炎症性疾病或感染以及脉络膜黑色素瘤）的视网膜和虹膜中，VEGF染色也增加。在这些病例中，VEGF主要定位于视网膜神经元和视网膜色素上皮细胞内。此外，或者与其诱导NV的作用相关，VEGF可能在多种眼部疾病中导致BRB破坏，阻断VEGF信号传导可能有助于减轻某些类型的黄斑水肿。
