VEGF-initiated blood-retinal barrier breakdown in early diabetes.
VEGF-initiated blood-retinal barrier breakdown in early diabetes.
复制标题
DOI：
--
复制
发表时间：
2001-09
影响因子：
4.4
通讯作者：
Tamim Qaum;Qingwen Xu;Antonia M. Joussen;M. Clemens;Wenying Qin;K. Miyamoto;H. Hasséssian;S. Wiegand
中科院分区：
文献类型：
--
作者：
Tamim Qaum;Qingwen Xu;Antonia M. Joussen;M. Clemens;Wenying Qin;K. Miyamoto;H. Hasséssian;S. Wiegand
目的：(1)确定内源性血管内皮生长因子(VEGF)是否触发糖尿病血-视网膜屏障的破坏；(2)确定糖尿病视网膜高通透性血管的部位和表型。方法采用核糖核酸酶保护法测定1周糖尿病大鼠视网膜血管内皮细胞生长因子的表达。通过系统给药一种高度特异的中和血管内皮生长因子的可溶性Flt/F(C)结构(血管内皮生长因子TRapa(40))来阻断血管内皮生长因子的生物活性。IL 6受体失活的F(C)结构(IL6R Trap)作为同型对照。血-视网膜屏障的破坏使用伊文思蓝技术进行量化，并使用荧光微球进行空间定位。结果糖尿病1周组大鼠视网膜血管内皮生长因子基因表达水平是非糖尿病对照组的3.2倍(P<0.05)。在空间上，早期血-视网膜屏障的破坏局限于视网膜浅血管的视网膜小静脉和毛细血管。结论实验性糖尿病早期血-视网膜屏障破坏依赖于血管内皮生长因子，部分局限于视网膜内浅血管的小静脉和毛细血管。抑制血管内皮生长因子应该是治疗早期糖尿病血-视网膜屏障破坏的有效治疗方法。
PURPOSE The objectives of this study were to (1) determine whether endogenous vascular endothelial growth factor (VEGF) triggers diabetic blood-retinal barrier breakdown, and (2) identify the site as well as phenotype of the hyperpermeable diabetic retinal vessels. METHODS Retinal VEGF mRNA levels were quantified in 1-week diabetic rats using the RNase protection assay. VEGF bioactivity was blocked via the systemic administration of a highly specific VEGF-neutralizing soluble Flt/F(c) construct (VEGF TrapA(40)). An inactive IL6 receptor/F(c) construct (IL6R Trap) was used as an isotype control. Blood-retinal barrier breakdown was quantified using the Evans blue technique and was spatially localized with fluorescent microspheres. RESULTS Retinal VEGF mRNA levels in 1-week diabetic animals were 3.2-fold higher than in nondiabetic controls (P 0.05). Spatially, early blood-retinal barrier breakdown was localized to the retinal venules and capillaries of the superficial retinal vasculature. CONCLUSIONS Early blood-retinal barrier breakdown in experimental diabetes is VEGF dependent and is restricted, in part, to the venules and capillaries of the superficial inner retinal vasculature. VEGF inhibition should prove a useful therapeutic approach in the treatment of early diabetic blood-retinal barrier breakdown.