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A. Micera, A. Lambiase, A. Iovieno, R. Sgrulletta, S. Bonini, S. Bonini; Nerve Growth Factor (NGF) Modulates Tissue Remodeling in Vernal Keratoconjunctivitis (VKC) . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2668.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Factors involved in tissue remodeling such as collagen and metalloproteinases (MMPs) derived from activated fibroblasts are important pathogenic elements in VKC, a chronic inflammatory disorder of the ocular surface, characterized by conjunctival inflammation and fibrosis. Since NGF, a well–known pleiotrophic factor acting on cells belonging to the nervous, immune and visual systems, appears to modulate fibroblast functions, we evaluated the possible effect of NGF on primary cultures of VKC–derived fibroblasts. Methods: To investigate the possible contribution of NGF in VKC tissue remodeling, cultured VKC–derived conjunctival fibroblasts (n=3) were exposed to different concentrations of NGF and the expression of α–SMA, collagen type–I, –IV, –VII, and MMP–1–2–9 mRNA's were quantified and compared to healthy derived ones (n=3). Fibroblasts were first characterized for their trkANGFR, p75NTR and α–SMA protein expression at early passages (confocal analysis). NGF (0.4–4nM) or TGF–ß1 (1pM, the main profibrogenic factor) were added to fibroblast cultures for 6hrs/24hrs. α–SMA, procollagen, collagens, MMPs protein and mRNAs expression were quantified by ELISA/Western Blotting and relative real–time PCR respectively. Analysis of data was performed using ANOVA followed by Turkey–Kramer post hoc evaluation. Results: A significant increase of α–SMA expressing cell population outgrew from VKC biopsies (1.62–fold increase), associated with high rate collagen typeI/IV (rate: 7.78)was observed, in comparison to healthy ones (p<0.016). Neither NGF or TGF–ß1 exposure for 24 hrs influenced α–SMA expression, while NGF exposure for 6 days significantly decreased collagen type I expression (1.33–fold, p<0,05), an effect not observed with TGF–ß1 addition. NGF significantly increased MMP–9 mRNA and protein expression in a dose dependent manner (7.49–fold 0.4nM NGF and 24.50–fold 4nM NGF after 6hrs, p<0.05). Conclusions: NGF appears to down–regulate the expression of collagen type I and to up–regulate MMP–9 mRNA/protein expression. Taken together, our findings suggest that NGF might contribute to fibrosis and tissue remodelling by influencing VKC fibroblasts collagen and MMPs production.
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