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Establishment of a Clinically Relevant Ex Vivo Mock Cataract Surgery Model for Investigating Epithelial Wound Repair in a Native Microenvironment
Published on: June 5, 2015
Molecular cell biology for the refractive corneal surgeon: programmed cell death and wound healing
1Eye Institute, Cleveland Clinic Foundation, OH 44195, USA.
Background:
Variability of outcome following refractive surgical procedures is affected by corneal wound healing. Interactions between the corneal epithelium and stromal keratocytes affect both stromal remodeling and healing of the epithelium. These processes contribute to regression of initial effect, surface irregularity, and stromal scarring that occur following excimer laser photorefractive keratectomy (PRK). I review recent discoveries related to stromal-epithelial molecular interactions that provide insights into the cellular responses to refractive surgical procedures.
Results:
Injury to the corneal epithelium stimulates programmed cell death (apoptosis) of the underlying anterior stromal keratocytes. I hypothesize that apoptosis of the keratocytes occurring immediately after epithelial injury associated with refractive surgical procedures initiates the subsequent wound healing response. Activated keratocytes subsequently repopulate the anterior corneal stroma where they produce collagen and other components associated with stromal remodeling. In addition, secretion of hepatocyte growth factor and keratinocyte growth factor by keratocytes increases after corneal epithelial wounding and these growth factors stimulate proliferation and inhibit differentiation of epithelial cells, effects which could promote epithelial hyperplasia associated with regression after photorefractive keratectomy.
Conclusion:
Corneal stromal-epithelial interactions help explain the different results that occur following excimer laser photorefractive keratectomy and laser in situ keratomileusis.
Insights
Corneal wound healing after refractive surgery involves stromal-epithelial interactions. These interactions, including keratocyte apoptosis and growth factor release, influence healing and outcomes like regression and scarring after photorefractive keratectomy (PRK).
Area of Science:
- Ophthalmology
- Cell Biology
- Regenerative Medicine
Background:
- Corneal wound healing significantly impacts outcomes of refractive surgical procedures.
- Stromal-epithelial cell interactions are crucial for corneal remodeling and epithelial healing.
- These interactions influence post-photorefractive keratectomy (PRK) complications such as regression, surface irregularity, and scarring.
Purpose of the Study:
- To review recent discoveries on molecular interactions between corneal stromal and epithelial cells.
- To provide insights into cellular responses following refractive surgery.
- To elucidate the mechanisms underlying corneal healing and visual outcome variability.
Main Methods:
- Review of recent scientific literature on corneal wound healing and stromal-epithelial interactions.
- Analysis of molecular signaling pathways involved in cellular responses to refractive surgery.
- Integration of findings to explain clinical observations post-PRK.
Main Results:
- Epithelial injury triggers apoptosis in anterior stromal keratocytes, initiating the wound healing cascade.
- Activated keratocytes repopulate the stroma, producing collagen and remodeling matrix components.
- Keratocyte-derived growth factors (HGF, KGF) stimulate epithelial cell proliferation and inhibit differentiation, potentially causing hyperplasia and regression post-PRK.
Conclusions:
- Corneal stromal-epithelial interactions are key to understanding variable outcomes after refractive surgery.
- These interactions explain differences observed between photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK).
- Understanding these cellular mechanisms can guide strategies to improve refractive surgery results.
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