The Key Role of Insulin-Like Growth Factor I in Limbal Stem Cell Differentiation and the Corneal Wound-Healing Process

Trošan, Peter; Svobodová, Eliška; Chudíčková, Milada; Krulová, Magdaléna; Zajı́cová, Alena; Holáň, Vladimı́r

doi:10.1089/scd.2012.0180

Cited by 68 publications

(42 citation statements)

References 37 publications

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“…The frozen corneal tissue was then homogenized and added in 500 μ L of TRI Reagent (Molecular Research Center, Cincinnati, OH) for the RNA isolation. The details of RNA isolation, transcription, and the PCR parameters have been described previously [13]. In brief, total RNA was extracted using TRI Reagent according to the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

[Retracted] Molecular Hydrogen Effectively Heals Alkali‐Injured Cornea via Suppression of Oxidative Stress

Čejka

Kössl

Heřmánková

et al. 2017

Oxidative Medicine and Cellular Longevity

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The aim of this study was to examine the effect of molecular hydrogen (H2) on the healing of alkali-injured cornea. The effects of the solution of H2 in phosphate buffered saline (PBS) or PBS alone topically applied on the alkali-injured rabbit cornea with 0.25 M NaOH were investigated using immunohistochemical and biochemical methods. Central corneal thickness taken as an index of corneal hydration was measured with an ultrasonic pachymeter. Results show that irrigation of the damaged eyes with H2 solution immediately after the injury and then within next five days renewed corneal transparency lost after the injury and reduced corneal hydration increased after the injury to physiological levels within ten days after the injury. In contrast, in injured corneas treated with PBS, the transparency of damaged corneas remained lost and corneal hydration elevated. Later results—on day 20 after the injury—showed that in alkali-injured corneas treated with H2 solution the expression of proinflammatory cytokines, peroxynitrite, detected by nitrotyrosine residues (NT), and malondialdehyde (MDA) expressions were very low or absent compared to PBS treated injured corneas, where NT and MDA expressions were present. In conclusion, H2 solution favorably influenced corneal healing after alkali injury via suppression of oxidative stress.

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Section: Methodsmentioning

confidence: 99%

[Retracted] Molecular Hydrogen Effectively Heals Alkali‐Injured Cornea via Suppression of Oxidative Stress

Čejka

Kössl

Heřmánková

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…IGF-1 promotes corneal limbal stem cell differentiation into epithelial like cells in a mouse model of mechanical corneal damage. 40 Also, when combined with substance P, IGF-1 promotes corneal epithelial migration and has shown efficacy in treating patients with PCED. 30, 36, 38 Therefore the role of IGF-1 may be in differentiation and depend on other relevant factors and cellular interactions for corneal epithelial migration.…”

Section: Discussionmentioning

confidence: 99%

Human Growth Hormone Promotes Corneal Epithelial Cell Migration in Vitro

Ding

Wirostko

Sullivan

2015

Cornea

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Purpose Corneal wound healing is a highly regulated process that requires the proliferation and migration of epithelial cells and interactions between epithelial cells and stromal fibroblasts. Compounds that can be applied topically to the ocular surface and that have the capability of activating corneal epithelial cells to proliferate and/or migrate would be useful to promote corneal wound healing. We hypothesize that human growth hormone (HGH) will activate Signal Transducer and Activators of Transcription-5 (STAT5) signaling and promote corneal wound healing by enhancing corneal epithelial cell and fibroblast proliferation and/or migration in vitro. The purpose of this study is to test these hypotheses. Methods We studied cell signaling, proliferation and migration using an immortalized human corneal epithelial cell line and primary human corneal fibroblasts in vitro. We also examined whether insulin-like growth factor-1 (IGF-1), a hormone known to mediate many of HGH’s growth promoting actions, may play a role in this effect. Results We show that HGH activates STAT5 signaling and promotes corneal epithelial cell migration in vitro. The migratory effect requires an intact communication between corneal epithelia and fibroblasts, and is not mediated by IGF-1. Conclusion HGH may represent a topical therapeutic to promote corneal epithelial wound healing. This warrants further investigation.

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“…IGFs have important roles in growth and energy metabolism, and regulate cell migration (Lee et al, 2006), differentiation (Trosan et al, 2012), proliferation, and survival (Yanai et al, 2006) in corneal epithelial cells through insulin receptor, and IGF receptors type I and type II. IGF-I and its receptors are expressed by both human corneal keratocytes and epithelial cells (Li and Tseng, 1995).…”

Section: Corneal Epithelial Wound Healingmentioning

confidence: 99%

Progress in corneal wound healing

Ljubimov

Saghizadeh

2015

Progress in Retinal and Eye Research

616

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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The Key Role of Insulin-Like Growth Factor I in Limbal Stem Cell Differentiation and the Corneal Wound-Healing Process

Cited by 68 publications

References 37 publications

[Retracted] Molecular Hydrogen Effectively Heals Alkali‐Injured Cornea via Suppression of Oxidative Stress

[Retracted] Molecular Hydrogen Effectively Heals Alkali‐Injured Cornea via Suppression of Oxidative Stress

Human Growth Hormone Promotes Corneal Epithelial Cell Migration in Vitro

Progress in corneal wound healing

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