Chitosan Oligosaccharides Attenuates Oxidative-Stress Related Retinal Degeneration in Rats

被引:49
作者
Fang, I-Mo [1 ]
Yang, Chang-Hao [2 ]
Yang, Chung-May [2 ]
Chen, Muh-Shy [2 ]
机构
[1] Taipei City Hosp, Zhongxiao Branch, Dept Ophthalmol, Taipei, Taiwan
[2] Natl Taiwan Univ Hosp, Dept Ophthalmol, Taipei, Taiwan
来源
PLOS ONE | 2013年 / 8卷 / 10期
关键词
NF-KAPPA-B; WATER-SOLUBLE CHITOSAN; TRANSCRIPTION FACTOR; IN-VITRO; CELLS; BCL-2; GLUTATHIONE; APOPTOSIS; PROTEINS; EFFICACY;
D O I
10.1371/journal.pone.0077323
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
This study investigated the therapeutic potential and mechanisms of chitosan oligosaccharides (COS) for oxidative stress-induced retinal diseases. Retinal oxidative damage was induced in Sprague-Dawley rats by intravitreal injection of paraquat (PQ). Low-dose (5 mg/kg) or high-dose (10 mg/kg) COS or PBS was intragastrically given for 14 days after PQ injection. Electroretinograms were performed to determine the functionality of the retinas. The surviving neurons in the retinal ganglion cell layer and retinal apoptosis were determined by counting Neu N-positive cells in whole-mounted retinas and TUNEL staining, respectively. The generation of reactive oxygen species (ROS) was determined by lucigenin- and luminol-enhanced chemiluminescence. Retinal oxidative damages were assessed by staining with nitrotyrosine, acrolein, and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Immunohistochemical studies were used to demonstrate the expression of nuclear factor-kappa B (NF-kappa B) p65 in retinas. An in vitro study using RGC-5 cells was performed to verify the results. We demonstrated COS significantly enhanced the recovery of retinal function, preserved inner retinal thickness, and decreased retinal neurons loss in a dose-dependent manner. COS administration demonstrated anti-oxidative effects by reducing luminol-and lucigenin-dependent chemiluminenscense levels and activating superoxide dismutase and catalase, leading to decreased retinal apoptosis. COS markedly reduced retinal NF-kappa B p65. An in vitro study demonstrated COS increased I kappa B expression, attenuated the increase of p65 and thus decreased NF-kappa B/DNA binding activity in PQ-stimulated RGC-5 cells. In conclusion, COS attenuates oxidative stress-induced retinal damages, probably by decreasing free radicals, maintaining the activities of anti-oxidative enzymes, and inhibiting the activation of NF-kappa B.
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页数:16
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