Protective Effects of L-Carnitine Against Oxidative Injury by Hyperosmolarity in Human Corneal Epithelial Cells

Hua, Xin; Deng, Ran; Li, Jin; Chi, Wei; Su, Zhipeng; Lin, Jing; Pflugfelder, Stephen C.; Li, Dequan

doi:10.1167/iovs.14-16247

Cited by 58 publications

(46 citation statements)

References 45 publications

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“…The reason may be that the pro-inflammatory cytokines IL-1β and TNF-α just caused transient inhibition of stemness and the cell cycle, while hyperosmotic stress not only caused the suppression of stemness but also induced more severe cell apoptosis, necrosis, and a cell cycle arrested at the G2/M phase in CESCs, all of which are physiologic changes that cannot be recovered in a short time after treatment. In addition, several studies have demonstrated that hyperosmotic stress can raise the production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, TGF-β1, and IL-23) and chemokines (IL-8, CCL2, and CCL20) at mRNA and protein levels in human corneal epithelial cells [34,65]. Our findings also confirmed that hyperosmosis treatment promoted the expression of TNF-α, IL-1β, MCP-1, and IL-8 both in cultured corneal epithelial stem/progenitor cells and corneal injury mouse model.…”

Section: Discussionmentioning

confidence: 99%

Different Effects of Pro-Inflammatory Factors and Hyperosmotic Stress on Corneal Epithelial Stem/Progenitor Cells and Wound Healing in Mice

Yang

Zhang

Dong

et al. 2018

Stem Cells Translational Medicine

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Chronic inflammation and severe dry eye are two important adverse factors for the successful transplant of cultured limbal stem cells. The aim of this study was to investigate the effects of inflammation and hyperosmotic stress (a key pathological factor in dry eye) on corneal epithelial stem cells (CESCs) and corneal epithelial wound healing. We observed that the CESCs exhibited significant morphological changes when treated with interleukin‐1 beta (IL‐1β), tumor necrosis factor alpha (TNF‐α), or hyperosmotic stress. Colony‐forming efficiency or colony‐forming size was decreased with the increasing concentrations of IL‐1β, TNF‐α, or hyperosmotic stress, which was exacerbated when treated simultaneously with pro‐inflammatory factors and hyperosmotic stress. However, the colony‐forming capacity of CESCs recovered more easily from pro‐inflammatory factor treatment than from hyperosmotic stress treatment. Moreover, when compared with pro‐inflammatory factors treatment, hyperosmotic stress treatment caused a more significant increase of apoptotic and necrotic cell numbers and cell cycle arrest in the G2/M phase. Furthermore, the normal ability of corneal epithelial wound healing in the mice model was suppressed by both pro‐inflammatory factors and hyperosmotic stress treatment, and especially severely by hyperosmotic stress treatment. In addition, inflammation combined with hyperosmotic stress treatment induced more serious epithelial repair delays and apoptosis in corneal epithelium. Elevated levels of inflammatory factors were found in hyperosmotic stress‐treated cells and mice corneas, which persisted even during the recovery period. The results suggested that pro‐inflammatory factors cause transient inhibition, while hyperosmotic stress causes severe apoptosis and necrosis, persistent cell cycle arrest of CESCs, and severe corneal wound healing delay. Stem Cells Translational Medicine 2019;8:46–57

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Section: Discussionmentioning

confidence: 99%

Different Effects of Pro-Inflammatory Factors and Hyperosmotic Stress on Corneal Epithelial Stem/Progenitor Cells and Wound Healing in Mice

Yang

Zhang

Dong

et al. 2018

Stem Cells Translational Medicine

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“…L‐carnitine (Hua et al. ) and pterostilbene (Li et al. ), a blueberry component, were found to be able to reduce oxidative stress induced by hyperosmolarity in cultured cells.…”

Section: Preclinical Intervention Studiesmentioning

confidence: 99%

“…Both molecules were able to reduce the levels of oxidative damage biomarkers and inflammatory mediators, with associated reduction in the levels of antioxidant enzymes (Hua et al. ; Li et al. ).…”

Section: Preclinical Intervention Studiesmentioning

confidence: 99%

Dry eye disease and oxidative stress

Seen

Tong

2017

Acta Ophthalmologica

220

162

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Dry eye, an age-related condition, is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance and tear film instability. Environmental factors are also often implicated in dry eye including exposure to pollutants, ultraviolet (UV) radiation and ozone as well as the chronic use of preserved eyedrops such as in the treatment of glaucoma. These factors increase oxidative stress and ocular surface inflammation. Here, we reviewed the cellular, animal and clinical studies that point to the role of oxidative stress in dry eye disease. The biomarkers used to indicate oxidative damage in ocular surface tissues include 8-hydroxy-2 deoxyguanosine (8-OHdG), 4-hydroxynonenal (HNE) and malondialdehyde (MDD). Antioxidative defences in the ocular surface occur in the form of tear proteins such as lactoferrin and S100A proteins, and enzymes such as superoxide dismutase (SOD), peroxidase, catalase and mitochondrial oxidative enzymes. An imbalance between the level of reactive oxygen species (ROS) and the action of protective enzymes will lead to oxidative damage, and possibly inflammation. A small number of interventional studies suggest that oxidative stress may be directly targeted in topical therapy of dry eye treatment. For example, in vitro studies suggest that L-carnitine and pterostilbene, a blueberry component may reduce oxidative stress, and in animal studies, alpha-lipoic acid (ALP) and selenoprotein P may be helpful. Examples of treatments used in clinical trials include vitamin B12 eyedrops and iodide iontophoresis. With recent emphasis on ageing medicine and preventive holistic health, as well as the role of environmental science, research on oxidative stress in the ocular surface is likely to have increasing impact in the coming years.

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“…Osmoprotectants such as L-carnitine, erithritol, or betaine have been shown to significantly reduce HO-induced proinflammatory responses, 15 to promote the survival of corneal epithelial cells, and protect the integrity of the epithelium. [16][17][18] We therefore tested the effects of these molecules on wound healing under HO conditions ( Figure 5). Although L-carnitine and erithritol proved ineffective (Figures 5a and c), betaine showed a concentration-dependent improvement in HO wound healing (Figure 5b).…”

Section: Effects Of Osmoprotectants On Ho Cytotoxicity and Rgtasmentioning

confidence: 99%

Matrix regeneration agents improve wound healing in non-stressed human corneal epithelial cells

Robciuc

Arvola

Jauhiainen

et al. 2017

Eye

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PurposeMatrix regenerating agents (RGTAs) emerged as promising in vivo wound-healing agents. These agents could prove beneficial for the treatment of dry eye disease-associated corneal micro-erosions; therefore, we aimed to evaluate the wound healing efficacy of regenerative agents (RGTAs or serum) in an in vitro model of hyperosmolarity (HO) stressed and non-stressed human corneal epithelial cells.Patients and methodsThe migration and proliferation induced by the regenerative agents was evaluated using an in vitro scratch wound assay and brome-deoxy-uridine incorporation. The inflammatory profile and effects of osmoregulators were also investigated. The two-tailed paired t-test calculated the statistical significance, with P-value<0.05 considered significant.ResultsThe most efficient inducer of re-epithelization was 2% serum, followed closely by 2% RGTA with an average improvement in cell migration of 1.8- and 1.4-fold, respectively, when compared with the non-treated control. Hyperosmolar stress significantly reduced the restorative effects of both serum and RGTAs; these effects were, however, neutralized by the osmoregulator betaine.ConclusionThese findings suggest that RGTAs could provide efficient treatment for dry-eye associated corneal micro-lesions if ocular surface HO is neutralized.

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Protective Effects of L-Carnitine Against Oxidative Injury by Hyperosmolarity in Human Corneal Epithelial Cells

Abstract: Our findings demonstrate for the first time that L-carnitine protects HCECs from oxidative stress by lessening the declines in antioxidant enzymes and suppressing ROS production. Such suppression reduces membrane lipid oxidative damage markers and mitochondrial DNA damage.

Cited by 58 publications

References 45 publications

Different Effects of Pro-Inflammatory Factors and Hyperosmotic Stress on Corneal Epithelial Stem/Progenitor Cells and Wound Healing in Mice

Different Effects of Pro-Inflammatory Factors and Hyperosmotic Stress on Corneal Epithelial Stem/Progenitor Cells and Wound Healing in Mice

Dry eye disease and oxidative stress

Matrix regeneration agents improve wound healing in non-stressed human corneal epithelial cells

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