Prolonged exposure to high glucose impaired cellular behavior of normal human corneal epithelial cells

Fujita, Hiroki; Morita, Ikuo; Takase, Hiroshi; Ohno‐Matsui, Kyoko; Mochizuki, Manabu

doi:10.1076/ceyr.27.4.197.16598

Cited by 24 publications

(17 citation statements)

References 20 publications

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“…In this study, a close relationship was observed between the α , β values and Glu levels in 38-and 60-week-old OLETF rats, unlike the progression of type 2 diabetic mellitus Table 4 . This result supports the previous fi ndings for human diabetic keratopathy 41 .…”

Section: Scheme 1 the Function Of Cell Migration And Proliferation Insupporting

confidence: 93%

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Kinetic Analysis of the Rate of Corneal Wound Healing in Otsuka Long-Evans Tokushima Fatty Rats, a Model of Type 2 Diabetes Mellitus

et al. 2010

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Diabetic keratopathy is a well-known ocular complication secondary to type 2 diabetes mellitus. In this study, we performed a kinetic analysis of corneal wound healing in Long-Evans rats (normal rat) and Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus. Corneal wound healing in 7-week-old normal rats was mostly complete 24 h after corneal epithelial abrasion, and the process of corneal wound healing took place according to an equation with a fi rst-order rate constant. The rate of corneal wound healing in normal rats decreased with aging. The process of corneal wound healing in 38-and 60-week-old normal and OLETF rats occurred in two phases with rate constants for the fi rst and second phases represented as α and β, respectively. The α and β values in 38-and 60-week-old OLETF rats were lower than those in normal rats of the corresponding age. Furthermore, a close relationship was observed between the corneal wound healing rate constant and plasma glucose levels in OLETF rats. The present studies suggest the sequence of events that occur following damage to the corneal surface in OLETF rats as a model animal for a human type 2 diabetes mellitus.

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Section: Scheme 1 the Function Of Cell Migration And Proliferation Insupporting

confidence: 93%

“…40 . High glucose levels suppress the cellular behavior cell movement and proliferation of human corneal epithelial cells 41 . In addition, it has been reported that the instillation of insulin normalizes the delay in corneal wound healing in streptozotocin rats 12 .…”

Section: Scheme 1 the Function Of Cell Migration And Proliferation Inmentioning

confidence: 99%

Kinetic Analysis of the Rate of Corneal Wound Healing in Otsuka Long-Evans Tokushima Fatty Rats, a Model of Type 2 Diabetes Mellitus

et al. 2010

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“…47) High glucose levels suppress the proliferation of human corneal epithelial cells. 48) In addition, it has been reported that the instillation of insulin normalizes the delay in corneal wound healing in streptozotocin rats. 13) These previous reports show that the decrease in corneal wound healing in diabetic keratopathy is caused by a suppression of cell proliferation due to high glucose levels in tears.…”

Section: Discussionmentioning

confidence: 99%

“…This result supports the previous results for human diabetic keratopathy. 48) Therefore, OLETF rats may provide a useful model for studies to develop corneal woundhealing drugs for use in diabetic keratopathy resulting from type 2 diabetes mellitus.…”

Section: Discussionmentioning

confidence: 99%

Enhancing Effects of Sericin on Corneal Wound Healing in Otsuka Long-Evans Tokushima Fatty Rats as a Model of Human Type 2 Diabetes

Nagai

Murao

Ito

et al. 2009

Biological & Pharmaceutical Bulletin

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Diabetes mellitus is a common metabolic disorder that affects more than 190 million people worldwide.1,2) The prevalence of type 2 diabetes mellitus is increasing rapidly, and currently affects the health of millions of humans now, and will continue to do so in the near future. Among the factors that are responsible for the increasing prevalence of this disease are obesity, the consumption of energy-dense diets and low levels of physical activity.3) Type 2 diabetes results from the failure of pancreatic beta cells to adequately compensate for obesity and insulin resistance. 4)Ocular complications secondary to type 2 diabetes mellitus are a well-known cause of diabetic keratopathy. 5) Diabetic keratopathy is an entity that includes slow healing or loose adhesion of the corneal epithelium after wounding in diabetic patients. Histologically, it involves a thickening of the corneal epithelial basement membrane and morphologic changes in the corneal epithelium and endothelium. [6][7][8][9][10][11] Clinically, the damage to the corneal epithelium during vitreous surgery and retinal photocoagulation sometimes induces vision-threatening corneal complications, such as persistent epithelial defects in diabetic patients.12) It has been reported that such diabetic keratopathy is experienced by 50% or more of diabetic patients. 13)The corneal wound repair process involves cell adhesion, migration, proliferation, matrix deposition and tissue remodeling.14) Many of these biological processes are mediated by growth factors, cytokines and other mediators released in injured tissues or cells.15) These growth factors have been recognized as important mediators of proper wound repair, 16) and treatment with growth factors such as platelet-derived growth factor-BB, and recombinant human epidermal growth factor has been shown to be beneficial for patients with chronic pressure ulcers or non-healing diabetic ulcers. [17][18][19][20] However, for reasons of effectiveness, safety and stable supply, a potent wound-healing agent for human corneal wounds has not yet been introduced, and the development of effective and safe corneal wound-healing drugs is highly anticipated.Proteins such as fibroin and sericin are the main constituents of silk, with fibroin contributing 70 to 80% and sericin 20 to 30% of the total cocoon weight.21) When cocoons or raw silk are used for textiles, the sericin is mostly removed from the cocoon and disposed of unused. However, sericin has recently been investigated for its activities in biotechnological fields. 22,23) We reported that sericin instillation has a potent effect in promoting wound healing and wound-size reduction in rats.24) Therefore, it is possible that sericin may be applied as eye drops for corneal wound repair in diabetic patients. In this study, we investigated the enhancing effects of sericin on corneal wound healing in the debrided corneal epithelium of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model for human type 2 diabetes. MATERIALS AND METHODS Animals and Reagents Male Long-Eva...

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“…Moreover, direct structural and functional changes in the corneal epithelium were observed in diabetic patients and animals, which may not be related to neuropathy unless in severe disease (Rosenberg et al, 2000; Saghizadeh et al, 2001a; 2005; 2011; Quadrado et al, 2006; Chikama et al, 2007). Further, high glucose treatment mimicking the diabetic hyperglycemia has a fast and direct impact on the normal corneal epithelial cells and the epithelium of organ-cultured corneas decreasing cell adhesion and slowing down wound healing (Fujita et al, 2003; Tomomatsu et al, 2009; Xu et al, 2009; Yin and Yu, 2010). Additional studies should elucidate the degree and molecular mechanisms of the relationship between diabetic keratopathy and neuropathy.…”

Section: General Manifestations Of Diabetes In the Corneamentioning

confidence: 99%

Diabetic complications in the cornea

2017

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Diabetic corneal alterations, such as delayed epithelial wound healing, edema, recurrent erosions, neuropathy/loss of sensitivity, and tear film changes are frequent but underdiagnosed complications of both type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus. The disease affects corneal epithelium, corneal nerves, tear film, and to a lesser extent, endothelium, and also conjunctiva. These abnormalities may appear or become exacerbated following trauma, as well as various surgeries including retinal, cataract or refractive. The focus of the review is on mechanisms of diabetic corneal abnormalities, available animal, tissue and organ culture models, and emerging treatments. Changes of basement membrane structure and wound healing rates, the role of various proteinases, advanced glycation end products (AGEs), abnormal growth and motility factors (including opioid, epidermal, and hepatocyte growth factors) are analyzed. Experimental therapeutics under development, including topical naltrexone, insulin, inhibitors of aldose reductase and AGEs, as well as emerging gene and cell therapies are discussed in detail.

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Prolonged exposure to high glucose impaired cellular behavior of normal human corneal epithelial cells

Abstract: High glucose had deleterious effects on cellular behavior of HCEC, which might cause delayed corneal epithelial wound healing in diabetic keratopathy.

Cited by 24 publications

References 20 publications

Kinetic Analysis of the Rate of Corneal Wound Healing in Otsuka Long-Evans Tokushima Fatty Rats, a Model of Type 2 Diabetes Mellitus

Kinetic Analysis of the Rate of Corneal Wound Healing in Otsuka Long-Evans Tokushima Fatty Rats, a Model of Type 2 Diabetes Mellitus

Enhancing Effects of Sericin on Corneal Wound Healing in Otsuka Long-Evans Tokushima Fatty Rats as a Model of Human Type 2 Diabetes

Diabetic complications in the cornea

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