Doxycycline Ameliorates the Severity of Experimental Proliferative Vitreoretinopathy in Mice

After successful surgeries for patients with rhegmatogenous retinal detachment, the most common cause of retinal redetachment is proliferative vitreoretinopathy (PVR), which causes severe vision impairment and even blindness worldwide. Until now, the major treatment for PVR is surgical removal of th...

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Main Authors: Shun-Hua Chen, Yu-Jheng Lin, Li-Chiu Wang, Hsien-Yang Tsai, Chang-Hao Yang, Yu-Ti Teng, Sheng-Min Hsu
Format: Article
Language:English
Published: MDPI AG 2021-10-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/21/11670
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author Shun-Hua Chen
Yu-Jheng Lin
Li-Chiu Wang
Hsien-Yang Tsai
Chang-Hao Yang
Yu-Ti Teng
Sheng-Min Hsu
author_facet Shun-Hua Chen
Yu-Jheng Lin
Li-Chiu Wang
Hsien-Yang Tsai
Chang-Hao Yang
Yu-Ti Teng
Sheng-Min Hsu
author_sort Shun-Hua Chen
collection DOAJ
description After successful surgeries for patients with rhegmatogenous retinal detachment, the most common cause of retinal redetachment is proliferative vitreoretinopathy (PVR), which causes severe vision impairment and even blindness worldwide. Until now, the major treatment for PVR is surgical removal of the epiretinal membrane, while effective treatment to prevent PVR is still unavailable. Therefore, we investigated the potential of doxycycline, an antibiotic in the tetracycline class, to treat PVR using a mouse model. We used the human retinal pigment epithelial cell line, ARPE-19, for in vitro and in vivo studies to test doxycycline for PVR treatment. We found that doxycycline suppressed the migration, proliferation, and contraction of ARPE-19 cells with reduced p38 MAPK activation and total MMP activity. Intravitreal doxycycline and topical tetracycline treatment significantly ameliorated the PVR severity induced by ARPE-19 cells in mice. PVR increased the expression of MMP-9 and IL-4 and p38 MAPK phosphorylation and modestly decreased IL-10. These effects were reversed by doxycycline and tetracycline treatment in the mouse retina. These results suggest that doxycycline will be a potential treatment for PVR in the future.
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spelling doaj.art-8806277f6b544396bdb91f06fab6d6272023-11-22T20:55:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122211167010.3390/ijms222111670Doxycycline Ameliorates the Severity of Experimental Proliferative Vitreoretinopathy in MiceShun-Hua Chen0Yu-Jheng Lin1Li-Chiu Wang2Hsien-Yang Tsai3Chang-Hao Yang4Yu-Ti Teng5Sheng-Min Hsu6Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, TaiwanDepartment of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, TaiwanSchool of Medicine, I-Shou University, Kaohsiung 824, TaiwanDepartment of Ophthalmology, Tzu Chi Hospital, Taichung 427, TaiwanDepartment of Ophthalmology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 100, TaiwanDepartment of Ophthalmology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, TaiwanDepartment of Ophthalmology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, TaiwanAfter successful surgeries for patients with rhegmatogenous retinal detachment, the most common cause of retinal redetachment is proliferative vitreoretinopathy (PVR), which causes severe vision impairment and even blindness worldwide. Until now, the major treatment for PVR is surgical removal of the epiretinal membrane, while effective treatment to prevent PVR is still unavailable. Therefore, we investigated the potential of doxycycline, an antibiotic in the tetracycline class, to treat PVR using a mouse model. We used the human retinal pigment epithelial cell line, ARPE-19, for in vitro and in vivo studies to test doxycycline for PVR treatment. We found that doxycycline suppressed the migration, proliferation, and contraction of ARPE-19 cells with reduced p38 MAPK activation and total MMP activity. Intravitreal doxycycline and topical tetracycline treatment significantly ameliorated the PVR severity induced by ARPE-19 cells in mice. PVR increased the expression of MMP-9 and IL-4 and p38 MAPK phosphorylation and modestly decreased IL-10. These effects were reversed by doxycycline and tetracycline treatment in the mouse retina. These results suggest that doxycycline will be a potential treatment for PVR in the future.https://www.mdpi.com/1422-0067/22/21/11670doxycyclineproliferative vitreoretinopathy (PVR)rhegmatogenous retinal detachment (RRD)
spellingShingle Shun-Hua Chen
Yu-Jheng Lin
Li-Chiu Wang
Hsien-Yang Tsai
Chang-Hao Yang
Yu-Ti Teng
Sheng-Min Hsu
Doxycycline Ameliorates the Severity of Experimental Proliferative Vitreoretinopathy in Mice
International Journal of Molecular Sciences
doxycycline
proliferative vitreoretinopathy (PVR)
rhegmatogenous retinal detachment (RRD)
title Doxycycline Ameliorates the Severity of Experimental Proliferative Vitreoretinopathy in Mice
title_full Doxycycline Ameliorates the Severity of Experimental Proliferative Vitreoretinopathy in Mice
title_fullStr Doxycycline Ameliorates the Severity of Experimental Proliferative Vitreoretinopathy in Mice
title_full_unstemmed Doxycycline Ameliorates the Severity of Experimental Proliferative Vitreoretinopathy in Mice
title_short Doxycycline Ameliorates the Severity of Experimental Proliferative Vitreoretinopathy in Mice
title_sort doxycycline ameliorates the severity of experimental proliferative vitreoretinopathy in mice
topic doxycycline
proliferative vitreoretinopathy (PVR)
rhegmatogenous retinal detachment (RRD)
url https://www.mdpi.com/1422-0067/22/21/11670
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