Biological modulation of corneal epithelial wound healing

Loureiro, Renata Ruoco; Gomes, José Álvaro Pereira

doi:10.5935/0004-2749.20190016

Cited by 10 publications

(7 citation statements)

References 56 publications

(77 reference statements)

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“… 6 , 35 Proper wound repair is vital for corneal epithelial integrity and transparency. 36 , 37 Our work provides new insights into the corneal wound healing process and identifies the IFNβ-MMP13 axis as a potential therapeutic target to promote corneal regeneration.…”

Section: Discussionmentioning

confidence: 95%

dsRNA Induced IFNβ-MMP13 Axis Drives Corneal Wound Healing

Lan

Zhang

Zhu

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Purpose Cornea, the outermost transparent layer of the eye, is the first line of defense against external threats. Following injury, the wound healing response is crucial to corneal repair and regeneration, yet its underlying mechanism is poorly understood. Our study was designed to investigate the role of dsRNA and its regulatory network in corneal wound healing. Methods A corneal wound healing model was established via the surgical removal of half of the corneal surface and adjoining limbus. RNase III was then used to clarify the role of dsRNA in corneal wound closure and RNA-seq was performed to investigate the mechanism of dsRNA in the healing process. Related gene expression was assessed using immunofluorescence staining, qPCR, and Western blot. Flow cytometry and scratch assay were used to analyze the proliferation and migration of limbal stem/progenitor cells (LSCs) in vitro and functional analysis of the target genes was completed using the corneal wound healing model. Results Corneal wound healing was delayed and impaired when the dsRNAs were removed or damaged following RNase III digestion. The dsRNAs released following corneal damage activate type I interferon (IFN-I) signaling, primarily IFNβ, via the corneal epithelium and neutralizing IFNβ or blocking IFN-I signaling delays corneal wound closure. Moreover, our data identified MMP13 as a downstream effector of IFNβ where its expression promotes LSC proliferation and enhances corneal epithelial reconstruction in vivo. Conclusions The dsRNA induced IFNβ-MMP13 axis plays a key role in corneal wound healing.

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Section: Discussionmentioning

confidence: 95%

dsRNA Induced IFNβ-MMP13 Axis Drives Corneal Wound Healing

Lan

Zhang

Zhu

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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“…These factors include epidermal growth factor (EGF), HGF, KGF, insulin growth factor (IGF), and transforming growth factor a (TGF-a). Crosstalk between various growth factors provides cellular communication as part of the CE healing process [22,40].…”

Section: Growth Factorsmentioning

confidence: 99%

“…In an alkaline injury, recombinant human EGF promotes CECs proliferation and anti-inflammatory response [47]. TGF-a is another EGFR ligand and expressed by CECs; yet its receptor is expressed by fibroblasts [40]. TGF-a is a potent activator of CECs migration by mediating EGFR recycling, thus prolonging EGFR signaling [48].…”

Section: Epidermal Growth Factormentioning

confidence: 99%

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Wound healing of the corneal epithelium: a review

2021

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The corneal epithelium (CE) forms the outermost layer of the cornea. Despite its thickness of only 50 μm, the CE plays a key role as an initial barrier against any insults to the eye and contributes to the light refraction onto the retina required for clear vision. In the event of an injury, the cornea is equipped with many strategies contributing to competent wound healing, including angiogenic and immune privileges, and mechanotransduction. Various factors, including growth factors, keratin, cytokines, integrins, crystallins, basement membrane, and gap junction proteins are involved in CE wound healing and serve as markers in the healing process. Studies of CE wound healing are advancing rapidly in tandem with the rise of corneal bioengineering, which employs limbal epithelial stem cells as the primary source of cells utilizing various types of biomaterials as substrates.

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“…This healing process involves multiple cellular and molecular mechanisms, including cell migration and proliferation under the paracrine control of cytokines and growth factors in the different layers of the cornea [ 8 ]. Understanding such mechanisms and underlying molecular pathways is of paramount clinical importance to develop new therapeutic strategies aimed at fostering better, faster corneal healing and restoring ocular surface homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Shhedding New Light on the Role of Hedgehog Signaling in Corneal Wound Healing

Zhang

Mélik-Parsadaniantz

Baudouin

et al. 2022

IJMS

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The cornea, an anterior ocular tissue that notably serves to protect the eye from external insults and refract light, requires constant epithelium renewal and efficient healing following injury to maintain ocular homeostasis. Although several key cell populations and molecular pathways implicated in corneal wound healing have already been thoroughly investigated, insufficient/impaired or excessive corneal wound healing remains a major clinical issue in ophthalmology, and new avenues of research are still needed to further improve corneal wound healing. Because of its implication in numerous cellular/tissular homeostatic processes and oxidative stress, there is growing evidence of the role of Hedgehog signaling pathway in physiological and pathological corneal wound healing. Reviewing current scientific evidence, Hedgehog signaling and its effectors participate in corneal wound healing mainly at the level of the corneal and limbal epithelium, where Sonic Hedgehog-mediated signaling promotes limbal stem cell proliferation and corneal epithelial cell proliferation and migration following corneal injury. Hedgehog signaling could also participate in corneal epithelial barrier homeostasis and in pathological corneal healing such as corneal injury-related neovascularization. By gaining a better understanding of the role of this double-edged sword in physiological and pathological corneal wound healing, fascinating new research avenues and therapeutic strategies will undoubtedly emerge.

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Biological modulation of corneal epithelial wound healing

Cited by 10 publications

References 56 publications

dsRNA Induced IFNβ-MMP13 Axis Drives Corneal Wound Healing

dsRNA Induced IFNβ-MMP13 Axis Drives Corneal Wound Healing

Wound healing of the corneal epithelium: a review

Shhedding New Light on the Role of Hedgehog Signaling in Corneal Wound Healing

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