Doxycycline Prevents Matrix Remodeling and Contraction by Trichiasis-Derived Conjunctival Fibroblasts


LI, H; Ezra, DG; Burton, MJ; Bailly, M; (2013) Doxycycline Prevents Matrix Remodeling and Contraction by Trichiasis-Derived Conjunctival Fibroblasts. Investigative ophthalmology & visual science, 54 (7). pp. 4675-4682. ISSN 0146-0404 DOI: https://doi.org/10.1167/iovs.13-11787

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Abstract

PURPOSE. Trachoma is a conjunctival scarring disease, which is the leading infectious cause of blindness worldwide. Elimination of blinding trachoma is being held back by the high rate of trichiasis recurrence following surgery. There is currently no treatment available to suppress the profibrotic state and reduce recurrence. Although the mechanisms underlying trichiasis development are unknown, the profibrotic phenotype has been linked to matrix metalloproteinase (MMP) expression. Doxycycline, a well-known tetracycline antibiotic, can act as a broad MMP inhibitor and has showed some success in preventing fibrosis in various clinical contexts. The purpose of this work was to assess the antiscarring properties of doxycycline in an in vitro model of trichiasis fibroblast-mediated tissue contraction. METHODS. Primary cultures of fibroblasts were established from conjunctival samples obtained from normal donors or during surgery for trachomatous trichiasis. The effect of doxycycline on matrix contraction was investigated in our standard collagen gel contraction model. Cell morphology and matrix integrity were assessed using confocal reflection microscopy. Quantitative real time polymerase chain reaction and a FRET-based assay were used to measure MMP expression and activity, respectively. RESULTS. Doxycycline treatment successfully suppressed the contractile phenotype of trichiasis fibroblasts, matrix degradation, and significantly altered the expression of MMP1, MMP9, and MMP12 associated with the profibrotic phenotype. CONCLUSIONS. In view of the results presented here and the wider use of doxycycline in clinical settings, we propose that doxycycline might be useful as a treatment to prevent recurrence following trichiasis surgery.

Item Type: Article
Keywords: doxycycline, trichiasis, contraction, MMPs, glaucoma filtration surgery, controlled clinical-trial, trachomatous, trichiasis, gene-expression, metalloproteinases, inhibition, cytokine, matrix-metalloproteinase-9, 5-fluorouracil, neutrophils, Cell-Matrix Junctions, drug effects, Cells, Cultured, Collagen, drug effects, Conjunctiva, cytology, Doxycycline, pharmacology, Enzyme Inhibitors, pharmacology, Fibroblasts, drug effects, Humans, Matrix Metalloproteinase 1, metabolism, Models, Biological, Trachoma, drug therapy, metabolism, Trichiasis, drug therapy, metabolism
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
Research Centre: The International Centre for Evidence in Disability
International Centre for Eye Health
Neglected Tropical Diseases Network
PubMed ID: 23766479
Web of Science ID: 322637000033
URI: http://researchonline.lshtm.ac.uk/id/eprint/1229308

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