Oshima Yuji, Takahashi Kyoichi, Oshima Sachiko, Saishin Yoshitsugu, Saishin Yumiko, Silva Raquel Lima, Liang Xaoling, Reddy P Seshidhar, Ganesh Shanthi, Brann Terrence, Liau Gene, Kaleko Michael, Connelly Sheila, Campochiaro Peter A
Department of Ophthalmology, The Johns Hopkins University School of Medicine, Maumenee, Baltimore, Maryland 21287, USA.
J Cell Physiol. 2004 Jun;199(3):399-411. doi: 10.1002/jcp.10441.
Vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) have been implicated as important stimulatory factors for retinal neovascularization. In this study, we used intraocular gene transfer with gutless adenoviral (AGV) vectors to determine the effect of increased intraocular expression of VEGF, IGF-1, or sphingosine kinase (SPK), which produces sphingosine-1-phosphate, another angiogenic factor. Retinal neovascularization did not occur from intravitreous AGV-vectored VEGF, IGF-1, SPK, or combined VEGF and IGF-1, except occasionally adjacent to the retinal penetration site from the injection. However, corneal and iris neovascularization occurred after 2 weeks in all eyes injected with AGV.VEGF, but not those injected with only AGV.IGF-1 or AGV.SPK. These data suggest that the superficial capillary bed of the retina is relatively insensitive to VEGF, IGF-1, or SPK in adult mice, except when combined with retinal trauma. However, AGV-vectored VEGF is sufficient to consistently cause severe corneal and iris neovascularization. This provides a model for anterior segment neovascularization, which unlike previous models is relatively inexpensive and is not plagued by spontaneous regression, and therefore, may be useful for identification of new treatments.
血管内皮生长因子（VEGF）和胰岛素样生长因子-1（IGF-1）被认为是视网膜新生血管形成的重要刺激因子。在本研究中，我们使用无内脏腺病毒（AGV）载体进行眼内基因转移，以确定眼内VEGF、IGF-1或鞘氨醇激酶（SPK，可产生另一种血管生成因子鞘氨醇-1-磷酸）表达增加的影响。除了偶尔在注射部位附近的视网膜穿透点相邻处，玻璃体内AGV载体携带的VEGF、IGF-1、SPK或联合的VEGF和IGF-1均未引发视网膜新生血管形成。然而，在所有注射AGV.VEGF的眼中，2周后均出现角膜和虹膜新生血管形成，而仅注射AGV.IGF-1或AGV.SPK的眼中则未出现。这些数据表明，成年小鼠视网膜的浅表毛细血管床对VEGF、IGF-1或SPK相对不敏感，除非与视网膜损伤同时存在。然而，AGV载体携带的VEGF足以持续引发严重的角膜和虹膜新生血管形成。这为眼前段新生血管形成提供了一个模型，与以往模型不同的是，该模型相对便宜且不会出现自发消退的问题，因此可能有助于识别新的治疗方法。
