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

• Published in: International journal of ophthalmology Vol. 10; no. 6; pp. 890 - 895
• Main Authors: Xiong, Si-Qi, Jiang, Hai-Bo, Xu, Hui-Zhuo, Xia, Xiao-Bo
• Format: Journal Article
• Language: English
• Published: China International Journal of Ophthalmology Press 18.06.2017; Press of International Journal of Ophthalmology (IJO PRESS)
• Subjects: Basic Research; blood- retinal barrier; diabetic retinopathy; pyridone agent; diabetic retinopathy; blood-retinal barrier; pyridone agent
• ISSN: 2222-3959; 2227-4898
• DOI: 10.18240/ijo.2017.06.09

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.