Effect of topical administration of epidermal growth factor on healing of corneal epithelial defects in horses

Burling, Kristina; Seguin, Mary A.; Marsh, Peggy S.; Brinkman, Kathy; Madigan, John E.; Thurmond, Mark; Moon-Massat, Paula F.; Mannis, Mark J.; Murphy, Christopher J.

doi:10.2460/ajvr.2000.61.1150

Cited by 31 publications

(44 citation statements)

References 32 publications

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“…In their clinical study, EGF was applied topically to corneal ulcers involving the epithelial cell layer of the cornea. The study showed a dose‐dependent increase in healing using EGF that was limited by severe inflammation at 50 µg/mL 10 . EGF administration at 5 µg/mL showed neither inflammation nor promotion of wound healing.…”

Section: Discussionmentioning

confidence: 83%

“…Equine epithelial cell numbers increased by 147% after stimulation with 5 ng/mL. These results indicate that the effects of EGF in equine corneal cell cultures are advantageous and may have beneficial clinical effects despite the results of Burling's study 10 . In their clinical study, EGF was applied topically to corneal ulcers involving the epithelial cell layer of the cornea.…”

Section: Discussionmentioning

confidence: 94%

“…To date there have been no studies investigating the use of PDGF‐BB or TGF‐β in equine eyes. EGF has been used in one equine corneal ulcer clinical study, which failed to demonstrate significant evidence of accelerated healing 10 . The objectives of our study were to develop a methodology to culture equine epithelial cells and keratocytes, and subsequently to determine the in vitro effect of PDGF‐BB, TGF‐β1 and EGF on these cultured cells.…”

Section: Introductionmentioning

confidence: 99%

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Effects of growth factors (EGF, PDGF‐BB and TGF‐β1) on cultured equine epithelial cells and keratocytes: implications for wound healing

Haber

Cao

Panjwani

et al. 2003

Veterinary Ophthalmology

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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Effects of growth factors (EGF, PDGF‐BB and TGF‐β1) on cultured equine epithelial cells and keratocytes: implications for wound healing

Haber

Cao

Panjwani

et al. 2003

Veterinary Ophthalmology

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“…Although the growth factors, neurotrophins, fibronectin and cytokines accelerate corneal re-epithelialization, they have not been developed to clinical drugs. For example, epidermal growth factor accelerates corneal epithelial healing in a clinical trial (Pastor and Calonge, 1992), but corneal neovascularization was a risk factor (Yang et al, 2013; Burling et al, 2000). …”

Section: Introductionmentioning

confidence: 99%

Galectin-3 enhances extracellular matrix associations and wound healing in monkey corneal epithelium

Fujii

Shearer

Azuma

2015

Experimental Eye Research

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Poor healing of epithelial wounds in cornea is a major clinical problem, leading to persistent epithelial defects and ulceration. The primary cause is poor cell migration over the wound. Carbohydrate-binding protein galectin-3 binds to extracellular matrixes (ECMs) and promotes lamellipodia formation by cross-linking to α3 integrin. Recombinant galectin-3 also facilitates wound healing in the rodent cornea. The purposes of the present experiments were to: (1) establish epithelial wound healing models in monkey corneal explant culture, the models more relevant to human, (2) evaluate the healing effect of galectin-3 in our models, and (3) determine if galectin-3 enhances cell adhesion by interacting with ECMs on corneal surface and their ligand integrins. Monkey corneas with central wounds produced by sodium hydroxide (NaOH) or n-heptanol were incubated with or without recombinant galectin-3. The defected area was stained with sodium fluorescein. Primary isolated corneal epithelial cells from monkey were cultured with or without galectin-3 on plates coated with ECMs or integrins, and the number of adhering cells was counted. Galectin-3 expression in various eye tissues was visualized by immunoblotting. NaOH caused loss of epithelial cells and basement membrane. n-Heptanol removed epithelial cells, but the basement membrane was retained. These corneal defects spontaneously became smaller in a time-dependent manner. Exogenous galectin-3 enhanced wound healing in both NaOH and n-heptanol models. Galectin-3 also enhanced cell adhesion onto the major ECMs found in the basement and Bowman’s membranes and onto integrins. Relatively high levels of galectin-3 were detected in corneal and conjunctival epithelium, but tear fluid contained negligible galactin-3. These results suggested that the enhanced binding of epithelial cells to ECMs and integrins caused by galectin-3 might promote cell migration over wounded corneal surfaces. Since tear fluid contained relatively low levels of galectin-3, exogenous galectin-3 may be a beneficial drug to enhance re-epithelialization in human corneal diseases.

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“…documented the positive proliferative effects of exogenous EGF and PDGF-BB on both equine corneal epithelial cells and keratocytes in vitro [38]. EGF has been shown to increase cell proliferation and chemotactic migration [39, 40], and PDGF-BB increases matrix production and chemotaxis and enhances inflammatory reactions to accelerate tissue repair [38, 41]. EGF was a component of the naive fibroblast media and serum-free media and, therefore, its detection in all groups in this study was expected.…”

Section: Discussionmentioning

confidence: 99%

Effect of bone marrow-derived mesenchymal stem cells and stem cell supernatant on equine corneal wound healing in vitro

et al. 2017

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BackgroundWe aimed to determine and compare the in vitro effects of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) and mesenchymal stem cell supernatant (MSC-Sp) on the wound healing capacity of equine corneal fibroblasts using a scratch assay.MethodsBone marrow aspirates and eyes were collected from normal, euthanized horses with subsequent isolation and culture of BM-MSCs and corneal stromal cells. Corneal stromal cells were culture-expanded in the culture well of transwell plates and then treated with an autologous BM-MSC suspension (dose: 2.5 × 105/100 μL media with the BM-MSCs contained within the insert well), MSC-Sp solution, or naive culture media (control) for 72 h. A linear defect in confluent cell cultures was created (i.e., corneal scratch assay) to assess the cellular closure (“healing”) over time. Three representative areas of the scratch in each culture were photographed at each time point and the scratch area was quantitated using image analysis software (ImageJ). Media from the scratches were analyzed for various growth factors using human enzyme-linked immunosorbent assay (ELISA) kits that crossreact with the horse.ResultsThere was a significant percentage decrease in the scratch area remaining in the BM-MSC and MSC-Sp groups compared to the control group. There was also a significant percentage decrease in the scratch area remaining in the BM-MSC group compared to the MSC-Sp group at 36 h post-scratch and all time points thereafter. The concentration of transforming growth factor (TGF)-β1 in the media was significantly higher in the BM-MSC group compared to the control group.ConclusionsThe significant decrease in scratch area in equine corneal fibroblast cultures treated with autologous BM-MSCs compared to MSC-Sp or control treatments suggests that BM-MSCs may substantially improve corneal wound healing in horses. MSC-Sp may also improve corneal wound healing given the significant decrease in scratch area compared to control treatments, and would be an immediately available and cost-effective treatment option.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0577-3) contains supplementary material, which is available to authorized users.

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Effect of topical administration of epidermal growth factor on healing of corneal epithelial defects in horses

Abstract: Beneficial effects of topical administration of a high dose of EGF for acceleration of healing of corneal defects in eyes of horses are outweighed by the intensity of the associated inflammatory response.

Cited by 31 publications

References 32 publications

Effects of growth factors (EGF, PDGF‐BB and TGF‐β1) on cultured equine epithelial cells and keratocytes: implications for wound healing

Effects of growth factors (EGF, PDGF‐BB and TGF‐β1) on cultured equine epithelial cells and keratocytes: implications for wound healing

Galectin-3 enhances extracellular matrix associations and wound healing in monkey corneal epithelium

Effect of bone marrow-derived mesenchymal stem cells and stem cell supernatant on equine corneal wound healing in vitro

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