RRC ID 63812
著者 He H, Liang M, Li L, Luo S, Fang X, He H, Xiao X, Wu H, Lin Z.
タイトル PPAR-α Agonist Fenofibrate Suppressed the Formation of Ocular Surface Squamous Metaplasia Induced by Topical Benzalkonium Chloride.
ジャーナル Invest Ophthalmol Vis Sci
Abstract 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.
巻・号 61(3)
ページ 54
公開日 2020-3-9
DOI 10.1167/iovs.61.3.54
PII 2764050
PMID 32232349
PMC PMC7401654
MeSH Animals Anti-Infective Agents, Local / toxicity Benzalkonium Compounds / toxicity Calcium-Binding Proteins / metabolism Cell Count Cell Line Cell Survival Disease Models, Animal Epithelium, Corneal / drug effects* Epithelium, Corneal / metabolism Epithelium, Corneal / pathology Fenofibrate / pharmacology* Humans Hypolipidemic Agents / pharmacology* Immunohistochemistry Interleukin-6 / genetics Keratin-10 / metabolism Ki-67 Antigen / metabolism Male Metaplasia / chemically induced Metaplasia / drug therapy Metaplasia / metabolism Metaplasia / pathology Mice Mice, Inbred BALB C PPAR alpha / agonists* Real-Time Polymerase Chain Reaction Receptors, G-Protein-Coupled / metabolism Tumor Necrosis Factor-alpha / genetics
IF 3.47
リソース情報
ヒト・動物細胞 HCE-T(RCB2280)