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Effect of pyridone agent on blood-retinal barrier in diabetic mice

Effect of pyridone agent on blood-retinal barrier in diabetic mice

作     者:Si-Qi Xiong Hai-Bo Jiang Hui-Zhuo Xu Xiao-Bo Xia Si-Qi Xiong Hai-Bo Jiang Hui-Zhuo Xu Xiao-Bo Xia

作者机构:Department of Ophthalmology Xiangya Hospital Central South University Changsha 410008 Hunan Province China 

出 版 物:《International Journal of Ophthalmology(English edition)》 (国际眼科杂志(英文版))

年 卷 期:2017年第10卷第6期

页      面:890-895页

核心收录:

学科分类:1002[医学-临床医学] 100201[医学-内科学(含:心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 100212[医学-眼科学] 10[医学] 

基  金:Supported by National Natural Science Foundation of China(No.81000388) Health and Family Planning Commission of Hunan Province(No.132015-016) Natural Science Foundation of Hunan Province(No.12JJ3120) 

主  题:pyridone agent diabetic retinopathy blood-retinal barrier 

摘      要:AIM: To evaluate the therapeutic effect of fluorofenidone on disrupted blood-retinal barrier in the diabetic mice and uncover its underlying mechanism. METHODS: 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-I) 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. RESULTS: 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-l, 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. CONCLUSION: 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.

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