Growth factors in corneal wound healing following refractive surgery: A review

Baldwin, Heather; Marshall, John

doi:10.1034/j.1600-0420.2002.800303.x

Cited by 105 publications

(89 citation statements)

References 101 publications

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“…Several researchers have shown that growth factors such as EGF, TGF-β, bFGF, hepatocyte growth factor, PDGF, interleukin-6 and keratinocyte growth factor increase epithelial healing rates in vitro, but their in vivo effects after topical application are controversial (25). Some groups have reported that topical EGF application increased the wound-healing rate in vivo, but others reported no benefit.…”

Section: Discussionmentioning

confidence: 99%

“…After photorefractive keratectomy, the release of varying factors such as TGF-β, EGF, PDGF, vascular endothelial growth factor, hepatocyte growth factor and interleukin-6 has been reported. These growth factors have been further characterized by a recurrent set of events in a wound-healing context: injury-induced growth factor production and release, growth factor-induced proliferative and migratory re- sponses and morphologic changes in target cells, additional growth factor regulation through feedback loops and a specific termination process (25). Endogenous basic fibroblast growth factor (bFGF) levels, a member of the FGF family (26), have been shown to increase at injury sites (27).…”

Section: Discussionmentioning

confidence: 99%

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Caveolin-1 as a Novel Indicator of Wound-Healing Capacity in Aged Human Corneal Epithelium

Rhim

Kim

Yeo

et al. 2010

Mol Med

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Excess caveolin-1 has been reported to play a role in age-dependent hyporesponsiveness to growth factors in vitro. Therefore, we hypothesized that caveolin-1-dependent hyporesponsiveness to growth factors in aged corneal epithelial cells might be responsible for delayed wound healing in vivo. To test this hypothesis, we evaluated corneal wound-healing time by vital staining using fluorescein after laser epithelial keratomileusis (LASEK). We compared wound-healing times in young, middle-aged and elderly patients. We also examined caveolin-1 levels and other aging markers, such as p53 and p21, in the corneal epithelium. Elderly patients generally had higher caveolin-1 levels in the corneal epithelia than young patients. There were, however, variations among individuals with increased caveolin-1 in some young patients and decreased levels in some elderly patients. Wound-healing time after LASEK correlated well with the corneal caveolin-1 status. Therefore, we suggest that caveolin-1 status might be responsible for delayed wound healing in elderly patients after LASEK. Caveolin-1 status might be a regulator for wound-healing capacity and a novel target for in vivo adjustment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Caveolin-1 as a Novel Indicator of Wound-Healing Capacity in Aged Human Corneal Epithelium

Rhim

Kim

Yeo

et al. 2010

Mol Med

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“…Mechanical and/or surgical injury to the cornea triggers a wound healing response causing changes in extracellular matrix organization and cellular phenotype and density (Wilson et al, 2001;Jester et al, 1999a;Fini and Stramer, 2005). Numerous studies have shown that injury to the cornea facilitates release of multiple cytokines and growth factors from both corneal cells and the lacrimal glands (Fini, 1999;Mohan et al, 2003;Zieske, 2001;Baldwin and Marshall, 2002). Cytokines that have been shown to play important roles in maintaining corneal transparency and consequently clear vision are platelet-derived growth factor, transforming growth factor beta, fibroblast growth factor, and the interleukins (Jester et al, 1995;Jester et al, 2002;Girard et al, 1991;Masur et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

A novel method for generating corneal haze in anterior stroma of the mouse eye with the excimer laser

Mohan

Stapleton

Sinha

et al. 2008

Experimental Eye Research

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Refractive surgery is a popular method used to reduce or eliminate dependence on glasses and contact lenses. Corneal haze is one of the common complications observed after photorefractive keratectmomy (PRK). The objective of this study was to develop an in vivo mouse model that consistently produces moderate to severe corneal haze in the anterior stroma of the mouse cornea after excimer laser treatment to study myofibroblast biology and corneal wound healing in a genetically defined model. Regular-or irregular-phototherapeutic keratectomy (PTK) was performed on black C57BL/6 mice with the Summit Apex excimer laser (Alcon, Ft. Worth, TX). Different numbers of laser pulses (45; ablation depth ~10 μm) were fired on the central cornea, after scraping the epithelium prior to excimer laser ablation. Irregularity was generated by positioning a fine mesh screen in the path of laser after firing 50% of the pulses. Eyes were collected 1, 2, 3 or 4 weeks after the procedure. Haze formation was gauged with slit lamp biomicroscopy. Immunocytochemistry was used to determine number of myofibroblasts in the mouse cornea using antibodies specific for the myofibroblast marker alpha-smooth muscle actin (SMA). The numbers of SMA-positive cells/400X microscopic were determined by counting within the stroma. Statistical analysis was performed using analysis of variance (AVOVA) with the Bonferonni-Dunn adjustment for repeated measures. Regular-PTK with epithelial scrape (Group 3) and irregular-PTK with epithelial scrape (Group 4) in the mouse eyes were performed to produce corneal haze. Eyes collected 4 weeks after regular-or irregular-PTK after epithelial scrape showed 22 ± 6.6 (Group 3) or 34 ± 7.9 (Group 4) SMA-positive cells in the anterior cornea. The difference in the SMA-positive cells detected among the groups was statistically significant (p < 0.01). Less than 4 SMA-positive cells were detected in the tissue sections of the mouse eyes collected after 1, 2 or 3 weeks of regular (Group 3) or irregular PTK (Group 4) or controls (Group 1 and 2). The optimized PTK excimer laser conditions developed in this study produces haze selectively in anterior stroma of the mouse cornea immediately beneath the epithelial basement membrane. Irregular PTK performed after epithelial scrape by applying 45 laser pulses was found to be the most effective method to generate myofibroblasts. This PTK technique for inducing haze in mouse cornea in vivo provides a useful model for studying wound healing and myofibroblast biology in transgenic mice.

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“…The synthesis of new tissue requires proliferation, migration, and differentiation of epithelial cells, which are stimulated by growth factors secreted by keratocytes, epithelial growth factor (EGF), keratinocyte growth factor, and hepatocyte growth factor (Klenkler and Sheardown, 2004;Wilson et al, 1994). The synthesis of new tissue also requires proliferation of the remaining keratocytes (Zieske, 2000) that are regulated by EGF, TGF-b, platelet-derived growth factor, and fibroblast growth factor, secreted by epithelial and inflammatory cells (Baldwin and Marshall, 2002) and the synthesis of a new extracellular matrix secreted by fibroblasts.…”

Section: Introductionmentioning

confidence: 99%

Wound healing following refractive surgery in hens

Martínez-García¹,

Merayo‐Lloves

Blanco–Mezquita

et al. 2006

Experimental Eye Research

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The wound-healing response is critical to the outcome of refractive surgery and studying wound healing contributes to an understanding of the pathophysiology of other corneal injuries. Animal models allow research to be conducted with sufficient samples and under controlled parameters. We studied the hen to determine the healing process from clinical, biophysical, and biological standpoints after photorefractive keratectomy (PRK). PRK (ÿ6.0 diopters) was performed in hen eyes. At 3, 6, 12, 24, 48, and 72 h and 5, 7, 15, 30, and 60 days postoperatively, we studied the clinical follow-up, objective measurements of light transmission (direct transmittance), apoptosis by TUNEL assay, proliferation by immunocytochemical analysis of 5-bromo-2 0 -deoxyuridine, and expression of alpha smooth muscle actin (SMA) in myofibroblasts in the corneas. Hen corneas reepithelialize quickly. Haze developed from 5 to 60 days after surgery and was correlated with the appearance and finalization of the expression of SMA. The direct transmittance of light was low during the first 15 days and improved at 30 and 60 days. TUNEL-positive cells were observed 3 h after surgery and the numbers decreased thereafter. Epithelial proliferation began at 12 h and was greater at 48 h, while stromal cell proliferation began at 24 h and was greater at 72 h. The hen cornea is anatomically similar to the human cornea, and the manner in which it heals is a good model for studying different surgical techniques and pharmacologic assays.

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Growth factors in corneal wound healing following refractive surgery: A review

Cited by 105 publications

References 101 publications

Caveolin-1 as a Novel Indicator of Wound-Healing Capacity in Aged Human Corneal Epithelium

Caveolin-1 as a Novel Indicator of Wound-Healing Capacity in Aged Human Corneal Epithelium

A novel method for generating corneal haze in anterior stroma of the mouse eye with the excimer laser

Wound healing following refractive surgery in hens

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