The Therapeutic Effects and Possible Mechanism of Pranoprofen in Mouse Model of Corneal Alkali Burns.

Minting Chen,Yacouba Cissé,Lang Bai,Abdirahman Abdinasir Gureeye

doi:10.1155/2020/7485912

Abstract

Objective To investigate therapeutic effects and possible mechanism of pranoprofen in a mouse model of corneal alkali burns and provide new evidence for the clinical treatment of corneal alkali burns. Methods A unilateral alkali burn was created in the central cornea by placing a piece of 2 mm diameter filter paper soaked in 1N NaOH on the right eye for 30 seconds. After the model was performed, C57BL/6J mice received topical treatment with saline eye drops or pranoprofen eye drops and were, respectively, categorized as saline group and pranoprofen group, whereas the remaining normal mice that were not subjected to alkali burns served as control, each group containing 15 mice (n = 45). On the 5th day after model establishment, the corneal fluorescein sodium staining score was evaluated in order to assess corneal epithelial damage. Tissue HE stain was used to observe the pathological changes of corneal tissue in each group. Real-time RT-PCR and western blot were also performed to detect the mRNA and protein expression of NLRP3, IL-1β/p17, and matrix metallopeptidase MMP-13. Results 5 days after burns, microscopic observations of the pranoprofen group showed less corneal opacity and neovascularization development than the saline group. Sodium fluorescein staining showed obvious corneal structure disorders, poor corneal epithelium continuity, and a larger corneal epithelial defect area in the saline group (10.33±+−0.57) as opposed to the pranoprofen group (8.33 ± 0.57） (p < 0.05). HE stain results showed the saline group had obvious corneal structure disorder and the corneal epithelial layer was incomplete as opposed to the pranoprofen group. PCR and western blot results suggested that the pranoprofen group expressed less NLRP3, IL-1β, and MMP-13 mRNA and protein expression in corneal tissue than the saline group (p < 0.05). Conclusion Pranoprofen may alleviate inflammatory response by inhibiting the expression levels of NLRP3 and IL-1β at the early stage of corneal alkali injury, lowering the expression of MMP-13 and ultimately reducing corneal epithelial damage.

Highlights

Ocular chemical burns, considered as the main ophthalmic emergencies that require immediate assessment and intensive care, account for approximately 11.5%–22.1% of all ocular traumas [1]. e vast majority of the injuries occur in the workplace as a result of industrial accidents
At 5 days after burns, corneal opacity and formation of new blood vessels could be observed under the microscope, corneal epithelial defects can be seen by sodium fluorescein staining, and corneal epithelial defects could be noticed by HE staining; the PCR and western blot detected NLRP3, IL-1β, and Matrix metalloproteinase (MMP)-13 increased expression. ese findings are consistent with reports in the relevant literature
Pranoprofen can inhibit the expression of MMP-13, which is closely related to corneal neovascularization after burns

Summary

Introduction

Ocular chemical burns, considered as the main ophthalmic emergencies that require immediate assessment and intensive care, account for approximately 11.5%–22.1% of all ocular traumas [1]. e vast majority of the injuries occur in the workplace as a result of industrial accidents. Alkali materials are found more commonly in building materials and cleaning agents and occur more frequently than acid injuries [2]. Alkali agents are lipophilic and penetrate tissues more rapidly than acids [3, 4]. Ey possess the ability to saponify the fatty acids of cell membranes, penetrate the corneal stroma, and denature the structure of proteins, which results in cell decomposition and necrosis of eye tissues [5]. Present treatment measures include early irrigation, use of nutrients for cornea and artificial tears, antibiotics, cycloplegic agents, ophthalmic steroid, ascorbic acid, and surgical treatment. In addition to early irrigation in order to block the continuous damage of alkaline substances on the corneal surface, actively reducing inflammation response is one of the important measures to control this condition

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Conclusion