Effects of Keratinocyte Growth Factor-2 on Corneal Epithelial Wound Healing in a Rabbit Model of Carbon Dioxide Laser Injury

Wang, Xiaojie; Zhou, Xin; Ma, Jianchao; Tian, Haishan; Jiao, Yuchen; Zhang, Rui; Huang, Zhifeng; Xiao, Jian; Zhao, Binhai; Huan-wen, Qian; Li, Xiaokun

doi:10.1248/bpb.33.971

Cited by 23 publications

(13 citation statements)

References 24 publications

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“…27 It is well known that FGF-2 is a growth factor of corneal epithelial cells. 28,29 Loss of Notch 1 in the corneal Ϫ/Ϫ -Tg mice compared with that in the 8-week-old WT mice (n ϭ 6; P ϭ 0.0411). Comparison of the ratio of the epithelial cell layer thickness to the full corneal thickness measured at the central cornea (B).…”

Section: Discussionmentioning

confidence: 96%

Perlecan-Deficient Mutation Impairs Corneal Epithelial Structure

Inomata

Ebihara²,

Funaki³

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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Section: Discussionmentioning

confidence: 96%

Perlecan-Deficient Mutation Impairs Corneal Epithelial Structure

Inomata

Ebihara²,

Funaki³

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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“…In addition, the disruption of barrier function induced by hypoxia in human corneal epithelial cells was inhibited by KGF through ERK activation (Teranishi et al, 2008). Another member of the FGF family is KGF-2/FGF-10, which also functions in a paracrine fashion and has a role in regulation of corneal wound healing by stimulating epithelial stem cell proliferation (Wang et al, 2010b). …”

Section: Corneal Epithelial Wound Healingmentioning

confidence: 99%

Progress in corneal wound healing

Ljubimov

Saghizadeh

2015

Progress in Retinal and Eye Research

637

554

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Corneal wound healing is a complex process involving cell death, migration, proliferation, differentiation, and extracellular matrix remodeling. Many similarities are observed in the healing processes of corneal epithelial, stromal and endothelial cells, as well as cell-specific differences. Corneal epithelial healing largely depends on limbal stem cells and remodeling of the basement membrane. During stromal healing, keratocytes get transformed to motile and contractile myofibroblasts largely due to activation of transforming growth factor-β system. Endothelial cells heal mostly by migration and spreading, with cell proliferation playing a secondary role. In the last decade, many aspects of wound healing process in different parts of the cornea have been elucidated, and some new therapeutic approaches have emerged. The concept of limbal stem cells received rigorous experimental corroboration, with new markers uncovered and new treatment options including gene and microRNA therapy tested in experimental systems. Transplantation of limbal stem cell-enriched cultures for efficient re-epithelialization in stem cell deficiency and corneal injuries has become reality in clinical setting. Mediators and course of events during stromal healing have been detailed, and new treatment regimens including gene (decorin) and stem cell therapy for excessive healing have been designed. This is a very important advance given the popularity of various refractive surgeries entailing stromal wound healing. Successful surgical ways of replacing the diseased endothelium have been clinically tested, and new approaches to accelerate endothelial healing and suppress endothelial-mesenchymal transformation have been proposed including Rho kinase (ROCK) inhibitor eye drops and gene therapy to activate TGF-β inhibitor SMAD7. Promising new technologies with potential for corneal wound healing manipulation including microRNA, induced pluripotent stem cells to generate corneal epithelium, and nanocarriers for corneal drug delivery are discussed. Attention is also paid to problems in wound healing understanding and treatment, such as lack of specific epithelial stem cell markers, reliable identification of stem cells, efficient prevention of haze and stromal scar formation, lack of data on wound regulating microRNAs in keratocytes and endothelial cells, as well as virtual lack of targeted systems for drug and gene delivery to select corneal cells.

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“…FGF10, a member of the fibroblast growth factor family, is also known as keratinocyte growth factor 2 and promotes the growth, proliferation and differentiation of epithelial cells ( 12 , 13 ). It has also been reported to be an important growth factor in the regulation of corneal epithelial wound healing ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

Therapeutic efficacy of fibroblast growth factor 10 in a rabbit model of dry eye

Zheng

et al. 2015

Molecular Medicine Reports

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The aim of the present study was to investigate the therapeutic efficacy of fibroblast growth factor 10 (FGF10) in the promotion of healing, survival and expression of mucin in corneal epithelial cells in a rabbit dry eye model. A total of 12 healthy female New Zealand white rabbits were divided randomly into three groups. The lacrimal glands were injected with saline either alone (normal control group) or with concanavalin A (Con A), with either topical phosphate-buffered saline (PBS; PBS control group) or 25 µg/ml FGF10 (FGF10 treatment group). Lacrimal gland inflammation, tear function, corneal epithelial cell integrity, cell apoptosis and mucin expression were subsequently assessed. Lacrimal gland tissue biopsies were performed in conjunction with histology and electron microscopy observations. Tear meniscus height (TMH) and tear meniscus area (TMA) were measured using Fourier domain-optical coherence tomography. Tear membrane break-up time (TBUT) was also assessed and corneal fluorescein staining was performed. The percentages of apoptotic corneal and conjunctival (Cj) epithelial cells (ECs) were counted using a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method. The mRNA expression levels of Muc1 were determined using reverse transcription-quantitative polymerase chain reaction analyses. The TMH and TMA values of the PBS and treatment groups were found to be significantly reduced, compared with those of the normal control group 3 days after Con A injection. However, the TMH and TMA of the FGF10 treatment group were higher, compared with those of the PBS group 3 and 7 days after treatment, respectively. Furthermore, the FGF10 treatment group exhibited prolonged TBUT, reduced corneal fluorescein staining and repaired epithelial cell ultra-structure7 days after treatment. The percentages of apoptotic corneal- and Cj-ECs in the FGF10 treatment group were significantly reduced, compared with those in the PBS group. FGF10 significantly induced the mRNA expression of Muc1 in the corneal epithelial cells, compared with the normal control group, and induced higher mRNA expression levels of Muc1 in the Cj-ECs, compared with the PBS control group. In the present study, the rabbit dry eye model was successfully established 3 days after lacrimal gland Con A injection. FGF10 eye drops increased TMH and TMA, promoted corneal epithelial healing, reduced apoptosis of the corneal- and Cj-ECs and led to increased expression of Muc1.

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Effects of Keratinocyte Growth Factor-2 on Corneal Epithelial Wound Healing in a Rabbit Model of Carbon Dioxide Laser Injury

Cited by 23 publications

References 24 publications

Perlecan-Deficient Mutation Impairs Corneal Epithelial Structure

Perlecan-Deficient Mutation Impairs Corneal Epithelial Structure

Progress in corneal wound healing

Therapeutic efficacy of fibroblast growth factor 10 in a rabbit model of dry eye

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