Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined phenotypic changes during the wound healing process in the corneal epithelium of Goto-Kakizaki (GK) rats, a spontaneous model of type 2 diabetes mellitus. In this article, we provide an overview of our and other groups' research and describe the clinical features of diabetic keratopathy. We observed that the rate of corneal epithelial wound closure was decreased in GK rats compared with Wistar rats. Immunoreactivity for Cx43, K14, and Ki-67 was detected in the 2 layers of cells adjacent to the basement membrane in the corneal epithelium of GK rats, whereas only the single basal layer of cells was positive for these proteins in the corneal epithelium of Wistar rats. The frequency of Ki-67-positive cells was greater in GK rats than in Wistar rats in the intact corneal epithelium and during wound healing. The GK rat represents delayed corneal epithelial wound closure as well as that which is observed in human diabetic keratopathy. Furthermore, these results indicate a possibility of functional deviation in corneal epithelial cells with diabetes mellitus.
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PMID:Deviated mechanism of wound healing in diabetic corneas. 1788 21

An Otsuka Long-Evans Tokushima Fatty (OLETF) rat provides a useful model for studies to develop corneal wound healing drugs for use in diabetic keratopathy resulting from type 2 diabetes mellitus. We investigated the effects of sericin on corneal wound healing in OLETF rats. Corneal wounds were prepared by removal of the corneal epithelium and documented using a TRC-50X. Sericin was instilled into the eyes of rats five times a day following corneal abrasion. The plasma levels of glucose, triglycerides, cholesterol and insulin in 38 wk old OLETF rats were significantly higher than in normal control rats (LETO rats), and the rate of corneal wound healing in OLETF rats was slower than in normal rat, probably due to the suppression of cell migration and proliferation caused by high plasma glucose levels. The corneal wounds of OLETF rats instilled with saline showed almost complete healing 72 h after corneal epithelial abrasion. On the other hand, the instillation of sericin has a potent effect in promoting wound healing and wound size reduction in OLETF rats and the wounds showed almost complete healing at 48 h after abrasion. The sericin may be an effective and safe drug to promote corneal wound healing in diabetic keratopathy.
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PMID:Therapeutic effects of sericin on diabetic keratopathy in Otsuka Long-Evans Tokushima Fatty rats. 2437 18

Bullous keratopathy is a pathological corneal condition that arises due to irreversible oedema associated with endothelial cell loss or dysfunction. Symptoms may vary from mild (transient blurred vision and increased glare from epithelial oedema) to severe (an acute and significant loss of vision associated with frank endothelial decompensation, and pain due to ruptured epithelial bullae). Possible treatments to restore vision and minimise pain include topical hypertonic agents, bandage contact lenses, superficial anterior corneal surgical procedures or penetrating full thickness or endothelial keratoplasty. This case report describes a rare presentation of painless, bilateral, asymmetric bullous keratopathy with severe vision loss in an elderly male with non-insulin dependent diabetes mellitus.
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PMID:Painless bilateral bullous keratopathy. 2957 98

EPHX2 (encoding soluble epoxide hydrolase [sEH]) converts biologically active epoxyeicosatrienoic acids (EETs), anti-inflammatory and profibrinolytic effectors, into the less biologically active metabolites, dihydroxyeicostrienoic acids. We sought to characterize the expression and the function of EPHX2 in diabetic corneas and during wound healing. The expression of EPHX2 at both mRNA and protein levels, as well as sEH enzymatic activity, was markedly upregulated in the tissues/cells, including corneal epithelial cells as well as the retina of human type 2 and mouse type 1 (streptozotocin [STZ] induced) and/or type 2 diabetes. Ephx2 depletion had no detectable effects on STZ-induced hyperglycemia but prevented the development of tear deficiency. Ephx2-/- mice showed an acceleration of hyperglycemia-delayed epithelium wound healing. Moreover, inhibition of sEH increased the rate of epithelium wound closure and restored hyperglycemia-suppressed STAT3 activation and heme oxygenase-1 (HO-1) expression in the diabetic corneas. Treatment of diabetic corneas with cobalt protoporphyrin, a well-known HO-1 inducer, restored wound-induced HO-1 upregulation and accelerated delayed wound healing. Finally, Ephx2 depletion enhanced sensory innervation and regeneration in diabetic corneas at 1 month after epithelial debridement. Our data suggest that increased sEH activity may be a contributing factor for diabetic corneal complications; targeting sEH pharmacologically or supplementing EETs may represent a new, adjunctive therapy for treating diabetic keratopathy.
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PMID:Inhibition of Soluble Epoxide Hydrolase 2 Ameliorates Diabetic Keratopathy and Impaired Wound Healing in Mouse Corneas. 2961 40

We previously found the instillation of sericin to be useful as therapy for keratopathy with or without diabetes mellitus. In this study, we investigated whether a combination of solid magnesium hydroxide nanoparticles (MHN) enhances epithelial corneal wound healing by sericin using rabbits, normal rats and type 2 diabetes mellitus rats with debrided corneal epithelium (ex vivo and in vivo studies). Ophthalmic formulations containing sericin and MHN (N-Ser) were prepared using a bead mill method. The mean particle size of the N-Ser was 110.3 nm at the time of preparation, and 148.1 nm one month later. The instillation of N-Ser had no effect on the amount of lacrimal fluid in normal rabbits (in vivo), but the MHN in N-Ser was found to expand the intercellular space in ex vivo rat corneas. In addition, the instillation of N-Ser increased the phosphorylation of Extracellular Signal-regulated Kinase (ERK)1/2, a factor involved in cell adhesion and cell proliferation in the corneal epithelium, in comparison with the instillation of sericin alone. The combination with MHN enhanced epithelial corneal wound healing by sericin in rat debrided corneal epithelium (in vivo). This study provides significant information to prepare potent drugs to cure severe keratopathy, such as diabetic keratopathy.
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PMID:Therapeutic Potential of a Combination of Magnesium Hydroxide Nanoparticles and Sericin for Epithelial Corneal Wound Healing. 3110 18

Type 2 Diabetes Mellitus (T2DM) is reaching epidemic levels worldwide and with it, there is a significant increase in complications associated with the disease. T2DM affects virtually all organ systems including the eye. While frequently overlooked, diabetic keratopathy is the most common ocular complication of diabetes and can manifest in mild to severe forms, the latter of which poses a major threat to vision. As the initial barrier between the environment and the eye, the corneal epithelium functions in innate immune defense. Compromise of this barrier may predispose the cornea to infection and can hinder the refractive capabilities of the eye. The clinical burden in patients with diabetic keratopathy lies primarily in the inability of the corneal epithelium to repair damage and maintain its tight barrier function. Current therapies for diabetic keratopathy are supportive, centering on the prevention of infection and promotion of an optimal healing environment. With no clear disease-modifying agent identified as of yet, a thorough understanding of the pathophysiology that underlies the development of diabetic keratopathy at the cellular level is critical to identify and develop potential therapeutic agents capable of promoting corneal re-epithelialization to accelerate the wound healing process. The focus of this review is to examine what is known regarding the cellular and molecular mechanisms needed to maintain epithelial homeostasis and how it goes awry in diabetes.
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PMID:The impact of hyperglycemia on the corneal epithelium: Molecular mechanisms and insight. 3123 14