Abstract
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-κB) 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-κB p65. An in vitro study demonstrated COS increased IκB expression, attenuated the increase of p65 and thus decreased NF-κB/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-κB.
Highlights
The eye is a unique organ because of its constant exposure to oxidative stress such as radiation, atmospheric oxygen, environmental chemicals, and physical abrasion
Treatment with lowdose or high-dose of Chitosan oligosaccharides (COS) significantly enhanced the recovery of the b-wave ratio at day 3 (P
After counting the cells in inner nuclear layer (INL) and outer nuclear layer (ONL), the number of cells was significantly higher in the low-dose and high-dose COS treatment groups than in the PQ or PBStreated groups (P
Summary
The eye is a unique organ because of its constant exposure to oxidative stress such as radiation, atmospheric oxygen, environmental chemicals, and physical abrasion. Many ocular diseases, including glaucoma, age-related macular degeneration, and diabetic retinopathy are caused by oxidative stress [1,2,3,4]. Chitosan oligosaccharides (COS), the hydrolyzed product of chitosan, is a mixture of oligomers of β-1,4-linked dglucosamine residues and is abundant in the exoskeleton of crustaceans and in cell walls of fungi and insects [5]. Because it is readily soluble in water due to its shorter chain and absorbed through the intestine, COS can quickly enter the bloodstream and exert systemic therapeutic effects. The beneficial effects of COS on oxidative damages in vitro have been studied, the effects of COS on an animal model of experimentally induced retinal oxidative damages have not yet been explored
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