Related Experiment Video
Updated: Aug 8, 2026
A Human Corneal Organ Culture Model of Descemet's Stripping Only with Accelerated Healing Stimulated by Engineered Fibroblast Growth Factor 1
Published on: July 22, 2022
Nerve growth factor effect on human primary fibroblastic-keratocytes: possible mechanism during corneal healing
Alessandra Micera1, Alessandro Lambiase, Ilaria Puxeddu
1CIR Laboratory of Ophthalmology, University Campus Bio-Medico and G.B.Bietti, Foundation, Via Emilio Longoni 83, 00155 Rome, Italy.
Abstract:
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-beta1 (TGF-beta1) 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, trkA(NGFR) and p75(NTR) 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, trkA(NGFR) and p75(NTR) 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-beta1. 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.
Insights
Nerve growth factor (NGF) promotes corneal wound healing by influencing fibroblast-like keratocytes. NGF induces their differentiation, migration, and collagen gel contraction, supporting its therapeutic potential for corneal ulcers.
Area of Science:
- Ophthalmology
- Cell Biology
- Wound Healing Research
Background:
- Corneal injury triggers cytokine and growth factor responses, impacting epithelial-stromal interactions and potentially leading to fibrosis.
- Transforming growth factor-beta1 (TGF-beta1) is a key profibrotic factor, while nerve growth factor (NGF) is emerging as a modulator of wound healing and inflammation.
- NGF and its receptors (trkA/NGFR, p75/NTR) are present in the cornea, and NGF eye drops aid in healing certain corneal ulcers.
Purpose of the Study:
- To investigate the effects of NGF on fibroblastic-keratocytes during corneal healing, a process not previously studied.
- To determine if NGF influences the differentiation, migration, and matrix-remodeling activities of these cells.
Main Methods:
- Expression analysis of NGF, trkA/NGFR, and p75/NTR in fibroblastic-keratocytes.
- Assessing NGF's impact on fibroblastic-keratocyte differentiation into myofibroblasts.
- Evaluating NGF's effects on cell migration, Metalloproteinase-9 (MMP-9) expression and activity, and collagen gel contraction.
- Investigating NGF's influence on cell proliferation and collagen production.
Main Results:
- Fibroblastic-keratocytes express NGF, trkA/NGFR, and p75/NTR.
- NGF stimulated fibroblastic-keratocyte differentiation into myofibroblasts.
- NGF enhanced cell migration, MMP-9 expression/activity, and collagen gel contraction, without affecting proliferation or collagen production.
- A bidirectional regulatory relationship between NGF and TGF-beta1 on fibroblastic-keratocytes was observed.
Conclusions:
- NGF modulates key functional activities of fibroblastic-keratocytes, including differentiation, migration, and matrix contraction.
- These findings provide mechanistic insight into NGF's beneficial effects on corneal wound healing.
- NGF shows potential as a therapeutic agent for corneal repair, particularly in conditions involving fibroblastic-keratocyte activation.
Related Concept Videos
01:09Introduction to Fibroblasts
01:11Healing I: Introduction