Nerve growth factor has a modulatory role on human primary fibroblast cultures derived from vernal keratoconjunctivitis-affected conjunctiva

Alessandra Micera, Alessandro Lambiase, Barbara Stampachiacchiere, Roberto Sgruletta, Eduardo Maria Normando, Sergio Bonini, Stefano Bonini

Research output: Contribution to journalArticle

Abstract

Purpose: To evaluate the role of nerve growth factor (NGF) in remodeling processes of vernal keratoconjunctivitis (VKC). VKC is a chronic inflammatory disorder of the conjunctiva and is characterized by marked tissue remodeling. NGF, a pleiotrophic factor with documented profibrogenic activities, is produced by inflammatory and structural cells populating the VKC conjunctiva and is increased in the serum and tears of VKC patients. Methods: Primary cultures of VKC-derived fibroblasts (VKC-FBs) were exposed to increasing NGF concentrations (1-500 ng/ml) to evaluate and compare the expression of α-smooth muscle actin (αSMA, a defining myofibroblast marker), collagens (types I and IV), and metalloproteinases and tissue inhibitors (MMP9/TIMP1, MMP2/TIMP2) at the biochemical as well as molecular levels. Results: Endogenous NGF was increased in the VKC-FB supernatant, as compared to healthy-FB supernatant. VKC-FBs expressed αSMA and increased types I and IV collagens. VKC-FBs, and in particular all αSMA positive cells, expressed both trkANGFR and p75NTR, while healthy-FBs only expressed trkANGFR. Exogenous NGF did not change αSMA expression, while αSMA expression was enhanced by specific neutralization of p75NTR. NGF (10 ng/ml) exposure significantly decreased type I collagen expression, without affecting type IV collagen, and increased MMP9mRNA and protein. Conclusions: The autocrine modulation of differentiation and response of VKC-FBs to NGF exposure with downregulation of type I collagen and upregulation of MMP9 expression supports a relevant role for NGF in tissue remodeling of VKC.

Original languageEnglish
Pages (from-to)981-987
Number of pages7
JournalMolecular Vision
Volume13
Publication statusPublished - Jun 21 2007

ASJC Scopus subject areas

  • Ophthalmology

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    Micera, A., Lambiase, A., Stampachiacchiere, B., Sgruletta, R., Normando, E. M., Bonini, S., & Bonini, S. (2007). Nerve growth factor has a modulatory role on human primary fibroblast cultures derived from vernal keratoconjunctivitis-affected conjunctiva. Molecular Vision, 13, 981-987.