Inhibitory Effects of Plumbagin on Retinal Pigment Epithelial Cell Epithelial-Mesenchymal Transition In Vitro and In Vivo
Autor: | Hui-Fang Wang, Jianbin An, Hai-Ting Chen, Jingxue Ma, Qingli Shang |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Proliferative vitreoretinopathy Epithelial-Mesenchymal Transition Cell Motility Retinal Pigment Epithelium 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Plumbaginaceae In vivo Lab/In Vitro Research medicine Animals Epithelial–mesenchymal transition Cells Cultured Retinal pigment epithelium Chemistry Vitreoretinopathy Proliferative Retinal Epithelial Cells General Medicine Plumbagin medicine.disease Molecular biology eye diseases 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis sense organs Rabbits Naphthoquinones |
Zdroj: | Medical Science Monitor : International Medical Journal of Experimental and Clinical Research |
ISSN: | 1643-3750 1234-1010 |
Popis: | BACKGROUND This study aimed to explore the effects of plumbagin (PLB) on epithelial-to-mesenchymal transition in retinal pigment epithelial (RPE) cells and in proliferative vitreoretinopathy (PVR) rabbit models. MATERIAL AND METHODS Rabbit RPE cells were exposed to various concentrations (0, 5, 15, and 25 µM) of PLB. Motility, migration, and invasion of PLB-treated cells were determined in vitro using Transwell chamber assays and scratch wound assays. The contractile ability was evaluated by cell contraction assay. Expression of matrix metalloproteinases (MMPs) and epithelial-mesenchymal transition (EMT) markers were assessed by western blotting. Furthermore, PLB was injected in rabbit eyes along with RPE cells after gas compression of the vitreous. The presence of PVR was determined by indirect ophthalmoscopy on days 1, 7, 14, and 21 after injection. Also, optical coherence tomography (OCT), ultrasound images, electroretinograms (ERG), and histopathology were used to assess efficacy and toxicity. RESULTS PLB significantly inhibited the migration and invasion of RPE cells. The agent also markedly reduced cell contractive ability. Furthermore, PLB treatment resulted in the decreased expression of MMP-1, MMP2, α-SMA, and the protection of ZO-1. In addition, the PLB-treated eyes showed lower PVR grades than the untreated eyes in rabbit models. PLB exhibited a wide safety margin, indicating no evidence of causing retinal toxicity. CONCLUSIONS PLB effectively inhibited the EMT of rabbit RPE cells in vitro and in the experimental PVR models. The results open new avenues for the use of PLB in prevention and treatment of PVR. |
Databáze: | OpenAIRE |
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