Li Bin, Zhang Hai-Qing, Shi Yu, Min Yun-Bing, Lin Shao-Fen, Wu Kai-Li, Hu Jie, Tang Shi-Bo
Key Laboratory of Ophthalmology of the Ministry of Education and Zhong-Shan Ophthalmic Center, Sun Yet-Sun University, Guangzhou City, People's Republic of China.
Mol Vis. 2009;15:861-9. Epub 2009 Apr 27.
We performed human, animal, and in vitro studies to examine the potential role of nuclear transport factor 2 (NTF2) in conferring resistance to diabetic retinopathy (DR).
Blood NTF2 levels were assessed in two groups of patients with type 2 diabetes mellitus. Group P patients had a history of proliferative DR (PDR), while group N patients did not. The retinal vasculature was examined in diabetic rats three months after they received an intravitreal injection of a recombinant adeno-associated virus (rAAV) vector overexpressing NTF2 (rAAV2-NTF2). Control rats were treated with rAAV2 only. Rat retinal capillary endothelial cells (RRCECs) were infected with rAAV2-NTF2, or with a vector expressing siRNA targeted against NTF2, to assess the effects of overexpression and inhibition of NTF2 on vascular endothelial growth factor (VEGF) expression (mRNA and protein).
There was a strong trend for patients with DR to have lower blood NTF2 levels compared to those who did not have DR (0.10+/-0.01 versus 0.20+/-0.08, p=0.079). There was significantly less retinal blood vessel leakage in diabetic rats infected with rAAV2-NTF2 compared to controls (16.5+/-2.9 versus 24.7+/-7.3, p=0.039). These rats exhibited normal retinal vasculature and blood-retinal barrier function. VEGF expression was inhibited by NTF2 overexpression and stimulated by NTF2 inhibition, (protein [0.41+/-0.05 versus 0.23+/-0.06] and mRNA [0.37+/-0.04 versus 0.23+/-0.06] p<0.01 for all).
These finding suggest that NTF2 is a potential mediator of retinal vasculature integrity. NTF2 may act by altering VEGF expression, thereby influencing the development of DR in patients with diabetes mellitus.
我们进行了人体、动物和体外研究，以探讨核转运因子2（NTF2）在赋予糖尿病视网膜病变（DR）抗性方面的潜在作用。
对两组2型糖尿病患者的血液NTF2水平进行评估。P组患者有增殖性DR（PDR）病史，而N组患者没有。在糖尿病大鼠接受玻璃体内注射过表达NTF2的重组腺相关病毒（rAAV）载体（rAAV2-NTF2）三个月后，检查其视网膜血管系统。对照大鼠仅用rAAV2治疗。用rAAV2-NTF2或表达靶向NTF2的小干扰RNA（siRNA）的载体感染大鼠视网膜毛细血管内皮细胞（RRCEC），以评估NTF2过表达和抑制对血管内皮生长因子（VEGF）表达（mRNA和蛋白质）的影响。
与没有DR的患者相比，DR患者的血液NTF2水平有降低的强烈趋势（0.10±0.01对0.20±0.08，p = 0.079）。与对照组相比，感染rAAV2-NTF2的糖尿病大鼠视网膜血管渗漏明显减少（16.5±2.9对24.7±7.3，p = 0.039）。这些大鼠表现出正常的视网膜血管系统和血视网膜屏障功能。NTF2过表达抑制VEGF表达，而NTF2抑制则刺激VEGF表达（蛋白质[0.41±0.05对0.23±0.06]和mRNA[0.37±0.04对0.23±0.06]，所有p<0.01）。
这些发现表明NTF2是视网膜血管系统完整性的潜在调节因子。NTF2可能通过改变VEGF表达起作用，从而影响糖尿病患者DR的发展。
