Nerve growth factor effect on human primary fibroblastic-keratocytes: Possible mechanism during corneal healing

Alessandra Micera, Alessandro Lambiase, Ilaria Puxeddu, Luigi Aloe, Barbara Stampachiacchiere, Francesca Levi-Schaffer, Sergio Bonini*, Stefano Bonini*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


In response to corneal injury, cytokines and growth factors play a crucial role by influencing epithelial-stromal interaction during the healing and reparative processes which may resolve in tissue remodeling and fibrosis. While transforming growth factor-β1 (TGF-β1) is considered the main profibrogenic modulator of these process, recently the nerve growth factor (NGF) appears as a pleiotropic modulator of wound-healing and inflammatory responses. Interestingly in the cornea, where NGF, trkANGFR and p75NTR are expressed by epithelial cells and keratocytes, the NGF eye-drop induces the healing of neurotrophic or autoimmune corneal ulcers. During corneal healing, quiescent keratocytes are replaced by active fibroblast-like keratocytes/myofibroblasts. While the NGF effect on epithelial cells has been investigated, no data are reported for NGF effects on fibroblastic-keratocytes, during corneal healing. NGF, trkANGFR and p75NTR were found expressed by fibroblastic-keratocytes. NGF was able to induce fibroblastic-keratocyte differentiation into myofibroblasts, migration, Metalloproteinase-9 expression/activity and contraction of a 3D collagen gel, without affecting their proliferation and collagen production. These data also show a two-directional control of fibroblastic-keratocytes by NGF and TGF-β1. To sum up, the findings of this study indicate that NGF can modulate some functional activities of fibroblastic-keratocytes, thus substantiating the healing effects of NGF on corneal wound-healing.

Original languageAmerican English
Pages (from-to)747-757
Number of pages11
JournalExperimental Eye Research
Issue number4
StatePublished - Oct 2006

Bibliographical note

Funding Information:
We are grateful to Prof. Rita Levi-Montalcini for stimulating discussions and suggestions in our research. This work was supported by a grant from The Ministry of Health. A. Micera was the recipient of an EAACI fellowship 2002 (Bruxelles) for research abroad.


  • NGF
  • corneal healing
  • fibroblastic-keratocyte
  • metalloproteinases
  • tissue repair


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