A Proteomic Approach for Understanding the Mechanisms of Delayed Corneal Wound Healing in Diabetic Keratopathy Using Diabetic Model Rat

Yamamoto, Tetsushi; Otake, Hiroko; Hiramatsu, Noriko; Yamamoto, Naoki; Taga, Atsushi; Nagai, Noriaki

doi:10.3390/ijms19113635

Cited by 21 publications

(17 citation statements)

References 72 publications

(85 reference statements)

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“…STZ injection was first reported to have diabetogenic properties in 1963 and has since become a chemical widely used to model diabetes in experiments. Briefly for this model, rats are given daily injections of 160–240 mg/kg STZ for 2 days in order to mimic type I diabetes 1 5. The onset of hyperglycemia is rapid.…”

Section: Resultsmentioning

confidence: 99%

“…Yamamoto et al ’s study used shotgun liquid chromatography mass spectrometry to detect differentially expressed proteins in the cornea of STZ rats compared with controls 1. The study identified 188 proteins that were expressed at least twofold higher in STZ rats compared with controls and were serving as candidate proteins in the pathogenesis of delayed wound healing in diabetes.…”

Section: Resultsmentioning

confidence: 99%

“…Diabetes mellitus (DM) is an important chronic disease, affecting more than 342 million people worldwide, with a trend of increasing prevalence in the last decade. Patients with DM are at a higher risk of developing ocular complications and account for the major cause of acquired blindness in working-age populations 1–3. In recent years, much of the focus for public health system worldwide has been on secondary prevention of sight-threatening diabetic retinopathy.…”

Section: Introductionmentioning

confidence: 99%

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Experimental modeling of cornea wound healing in diabetes: clinical applications and beyond

Shih

Kwok

et al. 2019

BMJ Open Diab Res Care

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Diabetes mellitus is the most common cause of blindness in working age populations worldwide. While much of the focus for public health has been on secondary prevention in sight-threatening diabetic retinopathy, the cornea, including its epithelium and nerves, represents a major site of damage by chronic hyperglycemia. On injury, the diabetic cornea exhibits a delayed wound-healing response, as well as an altered ocular surface immune response. This suggests a potential association between the dysfunctional wound healing response and altered inflammation on the ocular surface. However, the presence of potential confounders makes this association difficult to investigate in human epidemiological studies. Thus, we turn to animal diabetic models for a better understanding.In this review, 20 original studies, published between 2008 and 2018, describe in vivo and in vitro models of diabetic cornea disease. We compared different models of diabetic cornea wound healing and discussed the relative strengths and drawbacks of each model. A number of molecular and cellular components involved in the corneal wound healing response that are altered in the presence of diabetes have been identified in the reviewed studies. Particularly, altered corneal epithelial protein concentrations of lumician and occludin were detected in diabetic eyes compared with controls. Additionally, the importance of IL-1β in modulating the inflammatory response after corneal injury in patients with diabetes and controls was further elucidated. Meanwhile, abnormal P2×7 receptor localization and decreased corneal sub-basal nerve density in diabetic eyes were shown to contribute to altered corneal nerve signaling after injury and thus affecting the wound healing response. Finally, the discovery of the therapeutic effects of topically administered aloe vera, Serpine 1, Resolvin D1 (RvD1), pigment epithelium-derived factor (PEDF) and Pro-His-Ser-Arg-Asn in diabetic animal models of cornea epithelial and nerve injury provide encouraging evidence for the future availability of effective treatment for diabetic keratopathy.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Experimental modeling of cornea wound healing in diabetes: clinical applications and beyond

Shih

Kwok

et al. 2019

BMJ Open Diab Res Care

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“…Interestingly, a C-terminal product of lumican, which can be generated for example by MT1-MMP cleavage ( Figure 5 ), has been shown to bind to ALK5 and promote corneal epithelial wound healing, increasing both epithelial cell migration and proliferation ( Yamanaka et al, 2013 ; Gesteira et al, 2017 ). Although lumican expression is important during the process of wound healing, persistent up-regulation of lumican beyond wound closure can lead to reduced adhesion of corneal epithelial basal cells, as seen in streptozotocin-induced diabetic rats ( Yamamoto et al, 2018 ).…”

Section: Keratan Sulfate Proteoglycans (Kspgs)mentioning

confidence: 99%

Distribution and Function of Glycosaminoglycans and Proteoglycans in the Development, Homeostasis and Pathology of the Ocular Surface

Puri

Coulson-Thomas

Gesteira

et al. 2020

Front. Cell Dev. Biol.

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The ocular surface, which forms the interface between the eye and the external environment, includes the cornea, corneoscleral limbus, the conjunctiva and the accessory glands that produce the tear film. Glycosaminoglycans (GAGs) and proteoglycans (PGs) have been shown to play important roles in the development, hemostasis and pathology of the ocular surface. Herein we review the current literature related to the distribution and function of GAGs and PGs within the ocular surface, with focus on the cornea. The unique organization of ECM components within the cornea is essential for the maintenance of corneal transparency and function. Many studies have described the importance of GAGs within the epithelial and stromal compartment, while very few studies have analyzed the ECM of the endothelial layer. Importantly, GAGs have been shown to be essential for maintaining corneal homeostasis, epithelial cell differentiation and wound healing, and, more recently, a role has been suggested for the ECM in regulating limbal stem cells, corneal innervation, corneal inflammation, corneal angiogenesis and lymphangiogenesis. Reports have also associated genetic defects of the ECM to corneal pathologies. Thus, we also highlight the role of different GAGs and PGs in ocular surface homeostasis, as well as in pathology.

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“…We previously used this methodology to evaluate changes in protein expression in the lens and cornea of STZ rats and found decreased superoxide dismutase. This decrease contributed to the progression of diabetic cataracts and overexpression of lumican, leading to delayed corneal wound healing in diabetic keratopathy-affected corneas (11,12).…”

Section: Introductionmentioning

confidence: 99%

Retinal proteomic evaluation of rats following streptozotocin‑injection using shotgun proteomics

et al. 2019

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it is important to elucidate how retinal stimulation leads to retinal protection and dysfunction. The current study aimed to identify factors that are up-and downregulated in the retinas of streptozotocin (STZ)-induced diabetic rats with acute retinal dysfunction. retinal function was measured and changes in protein expressions were determined using electroretinograms (erGs) and liquid chromatography/mass spectroscopy-based shotgun proteomics, respectively. The results revealed that the plasma glucose levels of STZ rats were markedly higher when compared with normal rats. Furthermore, levels of a-waves, b-waves and oscillatory potential amplitudes on erGs in STZ rats were decreased compared with healthy animals. With use of shotgun proteomics, 391 proteins were identified in the retinas of normal rats and 541 proteins were found in the retinas of STZ rats. Of the 560 proteins identified in rat retinas, 372 (66.4%) were present in both normal and STZ rats. of these, 19 (3.39%) were unique to normal rats and 169 (30.1%) were unique to STZ rats. Gene ontology analysis was performed on the candidate proteins that were differentially regulated in the retinas of STZ rats and focused on those classified as 'protein binding', which serve important roles in retinal neurodegeneration. The results revealed an excessive expression of retinol-binding protein 1 (rBP1) and a negative expression of rod outer segment membrane protein 1 (rom-1) in the retinas of STZ rats. Therefore, retinal function may be decreased with STZ-induced injury, and expressions of rom-1 and rBP1 may be altered in the retinas of STZ rats.

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A Proteomic Approach for Understanding the Mechanisms of Delayed Corneal Wound Healing in Diabetic Keratopathy Using Diabetic Model Rat

Cited by 21 publications

References 72 publications

Experimental modeling of cornea wound healing in diabetes: clinical applications and beyond

Experimental modeling of cornea wound healing in diabetes: clinical applications and beyond

Distribution and Function of Glycosaminoglycans and Proteoglycans in the Development, Homeostasis and Pathology of the Ocular Surface

Retinal proteomic evaluation of rats following streptozotocin‑injection using shotgun proteomics

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