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Xanthatin inhibits corneal neovascularization by inhibiting the VEGFR2mediated STAT3/PI3K/Akt signaling pathway

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Alkali burn is one of the main causes of corneal injury. The inflammation and neovascularization caused by alkali burns aggravate corneal damage, resulting in loss of vision. The aim of the present study was to evaluate the efficacy of xanthatin in the treatment of alkali burninduced inflammation and neovascularization. A CCK8 assay was used to detect the effects of different concentrations of xanthatin on the proliferation of human umbilical vein endothelial cells (HUVECs). The effects of xanthatin on the migration of HUVECs and the ability of lumen formation were examined using a scratch test and lumen formation assay, respectively. A total of 60 SpragueDawley rats were randomly divided into two groups to establish a corneal alkali burn model, and were treated with PBS and xanthatin eye drops four times a day. A slit lamp microscope recorded changes of the cornea at 0, 4, 7, 10 and 14 days, and the inflammatory indices of the cornea and the neovascular area were evaluated. The expression levels of vascular endothelial growth factor (VEGF) and pigment epitheliumderived factor (PEDF) in the cornea under different treatment conditions were detected using immunofluorescence and western blot analysis. In order to investigate the mechanism of xanthatin on the inhibition of inflammation and neovascularization, HUVECs were treated with xanthatin and PBS following VEGF treatment. The subcellular localization of signal transducer and activator of transcription 3 (STAT3) was detected using immunofluorescence. The expression levels of VEGF receptor 2 (VEGFR2), STAT3, phosphoinositide 3kinase (PI3K) and Akt were detected using western blot analysis. The results revealed that xanthatin inhibited the proliferation of HUVECs in a concentrationdependent manner. The migration ability and lumenforming ability of the HUVECs were also inhibited by xanthatin. Slit lamp microscopy showed that the inflammatory index and the area of neovascularization in the xanthatintreated group were significantly reduced, compared with those in the PBS treatment group. The xanthatin treatment group exhibited a lower protein expression level of VEGF and increased protein expression level of PEDF, compared with the PBS treatment group. In the VEGFtreated HUVECs, xanthatin significantly decreased the expression levels of pVEGFR2, phosphorylated (p)STAT3, pPI3K and pAkt. In conclusion, the present study confirmed that xanthatin inhibited corneal neovascularization and inflammation in the alkali burn model, elucidating the underlying mechanisms involved in its protective effects. Therefore, xanthatin may be a novel drug for the treatment of corneal alkali burn.
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Document Type: Research Article

Affiliations: 1: Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute, Nanchang, Jiangxi 330006, P.R. China 2: Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China 3: Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute, Nanchang, Jiangxi 330006, P.R. China 4: School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China 5: Eye Institute of Xiamen University, Xiamen, Fujian 361102, P.R. China

Publication date: January 1, 2018

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  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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