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Keratocyte-Derived Myofibroblasts: Functional Differences With Their Fibroblast Precursors
Ana C Acosta1, Hadi Joud1, Mei Sun1
1Cornea and External Disease, Department of Ophthalmology, University of South Florida, Tampa, Florida, United States.
Investigative Ophthalmology & Visual Science
|October 5, 2023
Summary
Fibroblasts and myofibroblasts exhibit distinct extracellular matrix production and functional behaviors, crucial for understanding corneal wound healing and scarring. These differences impact collagen deposition and cell migration.
Area of Science:
- Ophthalmology
- Cell Biology
- Biomaterials Science
Background:
- Corneal scarring is a significant cause of vision impairment.
- Understanding the cellular and matrix dynamics of corneal wound healing is crucial for developing effective treatments.
- Fibroblasts and myofibroblasts, derived from keratocytes, play distinct roles in tissue remodeling.
Purpose of the Study:
- To elucidate the functional differences between corneal fibroblasts and myofibroblasts.
- To compare extracellular matrix (ECM) composition and organization produced by these cell types.
- To investigate functional disparities in latent transforming growth factor-beta (TGF-β) activation, wound healing, and chemotaxis.
Main Methods:
- Utilized a novel triple transgenic mouse model (KeraRT/tetO-Cre/mTmG) for keratocyte lineage tracking.
- Induced myofibroblast differentiation from fibroblasts using TGF-β1.
- Analyzed ECM composition, collagen organization (via Second Harmonic Generation microscopy), and protein expression.
- Performed functional assays including latent TGF-β activation, in vitro wound healing, chemotaxis, and proliferation.
Main Results:
- Observed significant morphological differences between fibroblasts and myofibroblasts.
- Fibroblasts produced higher quantities of corneal collagens I and V, while myofibroblasts produced more fibronectin and non-collagenous ECM components.
- Demonstrated a significant difference in latent TGF-β activation between the two cell types.
- Identified distinct patterns in ECM synthesis, deposition, TGF-β activation, and chemotaxis.
Conclusions:
- Fibroblasts and myofibroblasts exhibit unique profiles in ECM production and functional activities.
- These distinct characteristics are likely critical for their respective roles during various phases of corneal wound healing.
- The findings provide insights into the cellular mechanisms underlying corneal scarring and potential therapeutic targets.
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