Comparison of therapeutic effects between topical 8-oxo-2′-deoxyguanosine and corticosteroid in ocular alkali burn model

Abstract

We compared the therapeutic effects of topical 8-oxo-2′-deoxyguanosine (8-oxo-dG) and corticosteroid in a murine ocular alkali burn model. (n = 128) The corneal alkali burn model was established by applying 0.1 N sodium hydroxide (NaOH), followed by treatment with 8-oxo-dG, 0.1% fluorometholone (FML), 1% prednisolone acetate (PDE), or phosphate-buffered saline (PBS) twice daily. One week later, the clinical and histological status of the cornea were assessed. Transcript levels of inflammatory cytokines and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase as well as the levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the cornea, were assayed. The 8-oxo-dG and PDE groups showed marked improvements in corneal integrity and clarity when compared with the PBS group (each p < 0.01). The numbers of cells stained for neutrophil elastase and F4/80-positive inflammatory cells were significantly decreased, with levels of interleukin(IL)-1β, IL-6, tumor necrosis factor(TNF)-α, and total ROS/RNS amounts markedly reduced in the 8-oxo-dG, FML, and PDE groups (each p < 0.05). Levels of NADPH oxidase type 2 and 4 were substantially more repressed in the 8-oxo-dG-treated group than in the PDE-treated group (each p < 0.05). Topical 8-oxo-dG showed excellent therapeutic effects that were comparable with those treated with topical PDE in a murine ocular alkali burn model.

Investigating the Anti-Inflammatory Effects of RCI001 for Treating Ocular Surface Diseases: Insight Into the Mechanism of Action

“…We speculate that the inhibitory effects of RCI001 on Rac1 mediate suppression of the NLRP3 inflammasome/IL-1β pathway, implicated in ROS generation via NADPH oxidase or TLR-related NF-κB activation ( 21 , 23 ) ( Figure 7 , presumed mechanism of RCI001 on the NLRP3 pathway). RCI001 was shown to modulate the activation of MAPK, ERK, and STAT pathways in the ocular alkali burn model ( 5 ). In the present study, we observed a discrepancy in the expression of Rac1, NLRP3, and caspase-1 between qPCR and western blotting ( Figures 5 , 6 ).…”

“…Corneal epithelial integrity was evaluated by administering 1 drop of 3% Lissamine Green B (Sigma-Aldrich) to the inferior lateral conjunctival sac and photographed using a Dino-Lite digital camera (Dino-Lite Pro, AnMo Electronics Corp, Hsinchu, Taiwan). Evaluation of corneal epithelial integrity and corneal clarity were performed by three blinded observers by the scoring systems as described elsewhere ( 5 , 17 ). Corneal epithelial integrity was scored using the following scale of 0 to 4 based on the intensity of corneal epithelial defects: 0 = no epithelial defect, 1 = less than 25% epithelial defect, 2 = 25–50% epithelial defect, 3 = 50–75% epithelial defect, and 4 = more than 75% epithelial defect ( 17 ).…”

“…We have previously shown that RCI001 dose-dependently promoted the corneal healing and inhibited inflammation in ethanol-induced and alkali burn ocular injury models ( 5 , 16 ). RCI001 suppressed neutrophil and macrophage infiltration in injured corneal tissues ( 5 , 16 ).…”

“…We have previously shown that RCI001 dose-dependently promoted the corneal healing and inhibited inflammation in ethanol-induced and alkali burn ocular injury models ( 5 , 16 ). RCI001 suppressed neutrophil and macrophage infiltration in injured corneal tissues ( 5 , 16 ). In addition, RCI001 was shown to improve ocular surface staining and tear secretion in mouse models of environmental- and inflammation-mediated DED ( 17 ).…”

“…Topical corticosteroids, cyclosporin A, and tacrolimus are effective therapeutic agents against ocular surface inflammatory diseases. However, topical corticosteroids have clinical limitations due to potential risks, such as secondary glaucoma, infection, and cataract formation ( 5 ). It should be noted that non-corticosteroid agents are not as potent as corticosteroids and cannot modulate innate immunity, a key regulator of ocular surface inflammation ( 6 , 7 ).…”