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PPAR-α Agonist Fenofibrate Suppressed the Formation of Ocular Surface Squamous Metaplasia Induced by Topical Benzalkonium Chloride

PURPOSE: To investigate the effects and mechanisms of the peroxisome proliferator-activated receptor alpha (PPAR-α) agonist fenofibrate on the formation of ocular surface squamous metaplasia induced by topical benzalkonium chloride (BAC) in a mouse model. METHODS: Ocular surface squamous metaplasia...

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Autores principales: He, Huan, Liang, Minghui, Li, Lan, Luo, Shunrong, Fang, Xie, He, Hui, Xiao, Xianwen, Wu, Huping, Lin, Zhirong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401654/
https://www.ncbi.nlm.nih.gov/pubmed/32232349
http://dx.doi.org/10.1167/iovs.61.3.54
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author He, Huan
Liang, Minghui
Li, Lan
Luo, Shunrong
Fang, Xie
He, Hui
Xiao, Xianwen
Wu, Huping
Lin, Zhirong
author_facet He, Huan
Liang, Minghui
Li, Lan
Luo, Shunrong
Fang, Xie
He, Hui
Xiao, Xianwen
Wu, Huping
Lin, Zhirong
author_sort He, Huan
collection PubMed
description PURPOSE: To investigate the effects and mechanisms of the peroxisome proliferator-activated receptor alpha (PPAR-α) agonist fenofibrate on the formation of ocular surface squamous metaplasia induced by topical benzalkonium chloride (BAC) in a mouse model. METHODS: Ocular surface squamous metaplasia was induced in 16 days by topical BAC application in mice. During the period of induction, mice were divided into four groups: no additional treatment (BAC+UT), topical vehicle (BAC+Vehicle), topical fenofibrate (BAC+Feno), or topical fenofibrate plus intraperitoneal injection of MK886 (BAC+Feno+MK886). The parameters of tear film were evaluated on day 16, and eye specimens were collected. Histologic investigation; PAS assays; immunostaining for cytokeratin 10 (K10), Ki67, and F4/80; and PCR assays for TNF-α and IL-6 were performed. Cell Counting Kit 8 (CCK-8) assays were performed to evaluate the inhibitory effects of fenofibrate on RAW264.7 cells. RESULTS: Fenofibrate suppressed the formation of BAC-induced instable tear film. In the BAC+Feno group, the expression of K10 and Ki67 was lower than in the other three groups. The number of goblet cells was reduced in eyes of the BAC+UT and BAC+Vehicle groups but was maintained in eyes of the BAC+Feno group. The number of F4/80-positive cells and the levels of TNF-α and IL-6 mRNA were significantly reduced in the cornea of the BAC+Feno group. These effects of fenofibrate could be attenuated by MK886. The cell viability of RAW264.7 cells could be significantly inhibited by fenofibrate in a dose-dependent pattern. CONCLUSIONS: Topical application of fenofibrate suppressed the formation of ocular surface squamous metaplasia, which might be mediated through the PPAR-α signaling pathway.
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spelling pubmed-74016542020-08-18 PPAR-α Agonist Fenofibrate Suppressed the Formation of Ocular Surface Squamous Metaplasia Induced by Topical Benzalkonium Chloride He, Huan Liang, Minghui Li, Lan Luo, Shunrong Fang, Xie He, Hui Xiao, Xianwen Wu, Huping Lin, Zhirong Invest Ophthalmol Vis Sci Cornea PURPOSE: To investigate the effects and mechanisms of the peroxisome proliferator-activated receptor alpha (PPAR-α) agonist fenofibrate on the formation of ocular surface squamous metaplasia induced by topical benzalkonium chloride (BAC) in a mouse model. METHODS: Ocular surface squamous metaplasia was induced in 16 days by topical BAC application in mice. During the period of induction, mice were divided into four groups: no additional treatment (BAC+UT), topical vehicle (BAC+Vehicle), topical fenofibrate (BAC+Feno), or topical fenofibrate plus intraperitoneal injection of MK886 (BAC+Feno+MK886). The parameters of tear film were evaluated on day 16, and eye specimens were collected. Histologic investigation; PAS assays; immunostaining for cytokeratin 10 (K10), Ki67, and F4/80; and PCR assays for TNF-α and IL-6 were performed. Cell Counting Kit 8 (CCK-8) assays were performed to evaluate the inhibitory effects of fenofibrate on RAW264.7 cells. RESULTS: Fenofibrate suppressed the formation of BAC-induced instable tear film. In the BAC+Feno group, the expression of K10 and Ki67 was lower than in the other three groups. The number of goblet cells was reduced in eyes of the BAC+UT and BAC+Vehicle groups but was maintained in eyes of the BAC+Feno group. The number of F4/80-positive cells and the levels of TNF-α and IL-6 mRNA were significantly reduced in the cornea of the BAC+Feno group. These effects of fenofibrate could be attenuated by MK886. The cell viability of RAW264.7 cells could be significantly inhibited by fenofibrate in a dose-dependent pattern. CONCLUSIONS: Topical application of fenofibrate suppressed the formation of ocular surface squamous metaplasia, which might be mediated through the PPAR-α signaling pathway. The Association for Research in Vision and Ophthalmology 2020-03-30 /pmc/articles/PMC7401654/ /pubmed/32232349 http://dx.doi.org/10.1167/iovs.61.3.54 Text en Copyright 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
spellingShingle Cornea
He, Huan
Liang, Minghui
Li, Lan
Luo, Shunrong
Fang, Xie
He, Hui
Xiao, Xianwen
Wu, Huping
Lin, Zhirong
PPAR-α Agonist Fenofibrate Suppressed the Formation of Ocular Surface Squamous Metaplasia Induced by Topical Benzalkonium Chloride
title PPAR-α Agonist Fenofibrate Suppressed the Formation of Ocular Surface Squamous Metaplasia Induced by Topical Benzalkonium Chloride
title_full PPAR-α Agonist Fenofibrate Suppressed the Formation of Ocular Surface Squamous Metaplasia Induced by Topical Benzalkonium Chloride
title_fullStr PPAR-α Agonist Fenofibrate Suppressed the Formation of Ocular Surface Squamous Metaplasia Induced by Topical Benzalkonium Chloride
title_full_unstemmed PPAR-α Agonist Fenofibrate Suppressed the Formation of Ocular Surface Squamous Metaplasia Induced by Topical Benzalkonium Chloride
title_short PPAR-α Agonist Fenofibrate Suppressed the Formation of Ocular Surface Squamous Metaplasia Induced by Topical Benzalkonium Chloride
title_sort ppar-α agonist fenofibrate suppressed the formation of ocular surface squamous metaplasia induced by topical benzalkonium chloride
topic Cornea
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401654/
https://www.ncbi.nlm.nih.gov/pubmed/32232349
http://dx.doi.org/10.1167/iovs.61.3.54
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