RRC ID 71865
Author Yang Y, Huang C, Lin X, Wu Y, Ouyang W, Tang L, Ye S, Wang Y, Li W, Zhang X, Liu Z.
Title 0.005% Preservative-Free Latanoprost Induces Dry Eye-Like Ocular Surface Damage via Promotion of Inflammation in Mice.
Journal Invest Ophthalmol Vis Sci
Abstract Purpose:To investigate the side effects of preservative-free 0.005% latanoprost on the murine ocular surface.
Methods:We applied 0.005% latanoprost or vehicle in mice in two patterns for 14 to 28 days. Tear production was measured by phenol red cotton test, and corneal epithelial barrier function was assessed by Oregon-green-dextran (OGD) staining. Periodic acid-Schiff (PAS) staining was used to quantify conjunctival goblet cells (GCs). The expression of matrix metalloproteinase (MMP)-3 and -9, occludin-1 and zonula occludens (ZO)-1 in corneal epithelium was assessed by immunofluorescent staining and/or quantitative real-time PCR (qRT-PCR). Inflammation in conjunctiva was assessed by activation of P38 and NF-κB, infiltration of CD4+ T cells, and production inflammatory cytokines including TNF-α, IL-1β, IFN-γ, IL-17A, and IL-13. Apoptosis in ocular surface was assessed by TUNEL and immunofluorescent staining for activated caspase-3 and -8. Cell viability assay was performed in human corneal epithelial cells.
Results:Topical latanoprost treatment decreased tear production, induced conjunctival GC loss, disrupted the corneal epithelial barrier, and promoted cell apoptosis in the ocular surface. Topical latanoprost treatment increased the expression of MMP-3 and -9, and decreased the expression of ZO-1 and occludin-1 in the corneal epithelium. Topical application of latanoprost promoted activation of P38-NF-κB signaling and production of TNF-α and IL-1β in conjunctiva. Topical application of latanoprost increased CD4+ T cells infiltration, with increased production of IFN-γ and IL-17A and decreased production of IL-13 in conjunctiva.
Conclusion:0.005% latanoprost induced dry eye-like ocular surface damage via promotion of inflammation in mice.
Volume 59(8)
Pages 3375-3384
Published 2018-7-2
DOI 10.1167/iovs.18-24013
PII 2687704
PMID 30025085
MeSH Animals Antihypertensive Agents / administration & dosage Antihypertensive Agents / toxicity* Blotting, Western Conjunctivitis / chemically induced* Conjunctivitis / metabolism Conjunctivitis / pathology Cornea / drug effects* Cornea / metabolism Cornea / pathology Dry Eye Syndromes / chemically induced* Dry Eye Syndromes / metabolism Dry Eye Syndromes / pathology Enzyme-Linked Immunosorbent Assay Epithelium, Corneal / physiology Female Fluorescent Antibody Technique, Indirect Humans In Situ Nick-End Labeling Inflammation / chemically induced* Inflammation / metabolism Inflammation / pathology Latanoprost / administration & dosage Latanoprost / toxicity* Matrix Metalloproteinase 3 / genetics Matrix Metalloproteinase 3 / metabolism Matrix Metalloproteinase 9 / genetics Matrix Metalloproteinase 9 / metabolism Mice Mice, Inbred C57BL NF-kappa B / genetics NF-kappa B / metabolism Occludin / genetics Occludin / metabolism Preservatives, Pharmaceutical* Real-Time Polymerase Chain Reaction Tears / metabolism Zonula Occludens-1 Protein / genetics Zonula Occludens-1 Protein / metabolism p38 Mitogen-Activated Protein Kinases / genetics p38 Mitogen-Activated Protein Kinases / metabolism
IF 3.47
Human and Animal Cells HCE-T(RCB2280)