Xiong Si-Qi, Jiang Hai-Bo, Xu Hui-Zhuo, Xia Xiao-Bo
Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
Int J Ophthalmol. 2017 Jun 18;10(6):890-895. doi: 10.18240/ijo.2017.06.09. eCollection 2017.
To evaluate the therapeutic effect of fluorofenidone on disrupted blood-retinal barrier in the diabetic mice and uncover its underlying mechanism.
db/db mice were randomly chosen for treatment with daily doses of fluorofenidone or placebo at 5-week-old, treatment continued until mice reach 24-week-old. Then, expression of transcriptiona factor insulin gene enhancer binding protein-1 (Islet-1) and vascular endothelial growth factor (VEGF) in murine retinas were evaluated. Retinal vascular permeability was assessed by examining the level of albumin in db/db murine retinas. Furthermore, the retinal vessel tight junction was estimated by checking the level of occludin in the murine retinal tissues.
After occurrence of diabetic retinopthy in db/db mice, expressions of transcritpional factor Islet-1 was found to be upregulated in db/db murine retinas compared with non-diabetic controls. Similar to expression pattern of Islet-1, VEGF were also demonstrated to be increased in retinas of db/db mice, which was accompanied by increased retinal vascular leakage and decreased tight junction protein level. Systemetic administration of fluorofenidone repaired broken retinal vascular tight junction by restoring occludin expression in db/db retinal tissue. Consequently, retinal vascular premeability were indicated to be reduced by examining the transudative albumin level in diabetic retinal tissues. Both Islet-1 and VEGF expression were inhibited in the retinas of db/db mice after treatment with fluorofenidone.
Fluorofenidone significantly protectes retinal tight junction and reduces retinal vascular leakage. The phenomenon can be partially attributed to reducing overexpression of Islet-1 and VEGF in diabetic retinal tissues.
评估氟非尼酮对糖尿病小鼠血视网膜屏障破坏的治疗效果，并揭示其潜在机制。
选取5周龄的db/db小鼠，随机给予每日剂量的氟非尼酮或安慰剂治疗，持续治疗至小鼠24周龄。然后，评估小鼠视网膜中转录因子胰岛素基因增强子结合蛋白-1（Islet-1）和血管内皮生长因子（VEGF）的表达。通过检测db/db小鼠视网膜中白蛋白水平评估视网膜血管通透性。此外，通过检测小鼠视网膜组织中闭合蛋白水平评估视网膜血管紧密连接。
db/db小鼠发生糖尿病视网膜病变后，与非糖尿病对照组相比，db/db小鼠视网膜中转录因子Islet-1的表达上调。与Islet-1的表达模式相似，db/db小鼠视网膜中的VEGF也被证明增加，同时伴有视网膜血管渗漏增加和紧密连接蛋白水平降低。系统性给予氟非尼酮可通过恢复db/db视网膜组织中闭合蛋白的表达来修复受损的视网膜血管紧密连接。因此，通过检测糖尿病视网膜组织中的渗出性白蛋白水平表明视网膜血管通透性降低。用氟非尼酮治疗后，db/db小鼠视网膜中Islet-1和VEGF的表达均受到抑制。
氟非尼酮可显著保护视网膜紧密连接并减少视网膜血管渗漏。这种现象部分可归因于减少糖尿病视网膜组织中Islet-1和VEGF的过度表达。
