Involvement of advanced glycation end products, oxidative stress and nuclear factor-kappaB in the development of diabetic keratopathy

Kim, Jung-Hyun; Kim, Chan-Sik; Sohn, Eunjin; Jeong, Il-Ha; Kim, Hyojun; Kim, Jin Sook

doi:10.1007/s00417-010-1573-9

Cited by 73 publications

(71 citation statements)

References 39 publications

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“…These findings confirmed the high concentrations of the AGEs in corneal endothelium, and they suggested that the high expression of the AGEs in the iris and the aqueous humor may directly affect the corneal endothelium, subsequently leading to increased AGE expression [26]. The level of fluorescence is higher in diabetic corneas than in normal corneas because of the due AGEs [15]. Moreover, treatment with aminoguanidine, an AGEs inhibitor, prevented diabetic corneal structural abnormalities, such as the degeneration of intracellular organelles, cytoplasmic vacuole formation, and edema in the corneal stroma [27].…”

Section: Pathophysiology Of Diabetic Keratopa-thysupporting

confidence: 83%

“…The increased accumulation of the AGEs in diabetic corneas provided strong evidence that nuclear oxidative DNA damage caused by the accumulation of the AGEs is responsible for the apoptotic damage of corneal cells in diabetic patients ( Fig. 1) [15].…”

Section: Pathophysiology Of Diabetic Keratopa-thymentioning

confidence: 98%

“…Patients with diabetic keratopathy have impairments of the epithelial basement membrane (BM), epithelial wound healing, epithelial-stromal interactions, endothelial function, and corneal nerve functions [14]. The corneal disorders associated with diabetic keratopathy are characterized histologically by subepithelial deposits, and altered morphological appearances of the corneal epithelium and endothelium [15].…”

Section: Introductionmentioning

confidence: 99%

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Corneal Changes in Diabetes Mellitus

Bikbova¹,

Oshitari

Tawada³

et al. 2012

CDR

114

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Diabetes mellitus is a major disease worldwide, and the prevalence of diabetes has risen significantly in the past several decades. Although one of the major complications of diabetic eyes is diabetic retinopathy (DR), corneal diseases can not only develop in diabetic patients but are also difficult to manage. Diabetic neurotrophic keratopathy is a component of diabetic polyneuropathy and is recognized to be the cause of the morbidity of the cornea in diabetic patients. In addition, corneal endothelial cell damage can cause disturbances in the management of proliferative DR before and after surgeries because of endothelial decompensation with bullous keratopathy. However, there have been only a limited number of studies that have focused on the importance of corneal diseases in diabetic patients. This review describes the pathophysiological roles of different factors that have been found to be causative factors of diabetic corneal keratopathy and endothelial cell dysfunction in diabetic patients. In addition, the clinical features of the corneal changes in diabetic patients and recent studies related to the development of therapies for the management of corneal diseases are presented.

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Section: Pathophysiology Of Diabetic Keratopa-thysupporting

confidence: 83%

Section: Pathophysiology Of Diabetic Keratopa-thymentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Corneal Changes in Diabetes Mellitus

Bikbova¹,

Oshitari

Tawada³

et al. 2012

CDR

114

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“…Importantly, the diabetic corneal stroma accumulates AGEs, which may lead to collagen crosslinking and could contribute to increased central corneal thickness (Sady et al, 1995). This accumulation may also underlie changes in type IV collagen expression, impaired cell adhesion, and increased keratocyte apoptosis observed in mice with NIDDM and in rats with IDDM (Watanabe et al, 2002; Kim et al, 2011). In diabetic rats, stromal edema was also reported (Gül et al, 2008).…”

Section: General Manifestations Of Diabetes In the Corneamentioning

confidence: 99%

“…AGEs interact with their receptors (RAGEs) triggering intracellular signaling including NF-κB activation and formation of reactive oxygen species (ROS) (Kim et al, 2011; Shi et al, 2013a;b). Their accumulation in the diabetic corneal BMs and stroma may be responsible for clinically observed increased autofluorescence (Kaji et al, 2000; McDermott et al, 2003; Calvo-Maroto et al, 2016).…”

Section: Molecular Alterations and Disease Markers Of Diabetes In mentioning

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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Donor, Recipient, and Operative Factors Associated With Increased Endothelial Cell Loss in the Cornea Preservation Time Study

et al. 2019

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; for the Cornea Preservation Time Study Group IMPORTANCE Determining factors associated with endothelial cell loss after Descemet stripping automated endothelial keratoplasty (DSAEK) could improve long-term graft survival. OBJECTIVE To evaluate the associations of donor, recipient, and operative factors with endothelial cell density (ECD) 3 years after DSAEK in the Cornea Preservation Time Study. DESIGN, SETTING, AND PARTICIPANTS This cohort study was a secondary analysis of data collected in a multicenter, double-masked, randomized clinical trial. Forty US clinical sites with 70 surgeons participated, with donor corneas provided by 23 US eye banks. Individuals undergoing DSAEK for Fuchs dystrophy or pseudophakic/aphakic corneal edema were included. INTERVENTIONS The DSAEK procedure, with random assignment of a donor cornea with a preservation time of 0 to 7 days or 8 to 14 days. MAIN OUTCOMES AND MEASURES Endothelial cell density at 3 years as determined by a reading center from eye bank and clinical specular or confocal central endothelial images. RESULTS The study included 1090 participants (median age, 70 years) with 1330 affected eyes (240 bilateral cases [22.0%]), who underwent DSAEK for Fuchs dystrophy (1255 eyes [94.4%]) or pseudophakic/aphakic corneal edema (PACE) (75 eyes [5.6%]). Of these, 801 eyes (60.2%) belonged to women and 1207 (90.8%) to white individuals. A total of 749 participants (913 eyes; 164 [21.9%] bilateral cases) had functioning grafts with acceptable endothelial images preoperatively and at 3 years postoperatively and were included in this analysis. Factors associated with a lower ECD at 3 years (estimated effect with 99% CI) in the final multivariable model included donors with diabetes (−103 [−196 to −9] cells/mm 2), lower screening ECD (−234 [−331 to −137] per 500 cells/mm 2), recipient diagnosis of PACE (−257 [−483 to −31] in cells/mm 2), and operative complications (−324 [−516 to −133] in cells/mm 2). Endothelial cell loss (ECL) from a preoperative measurement to a 3-year postoperative measurement was 47% (99% CI, 42%-52%) for participants receiving tissue from donors with diabetes vs 43% (99% CI, 39%-48%) without diabetes; it was 53% (99% CI, 44%-62%) for participants diagnosed with PACE vs 44% (99% CI, 39%-49%) for those diagnosed with Fuchs dystrophy, and 55% (99% CI, 48%-63%) in participants who experienced operative complications vs 44% (99% CI, 39%-48%) in those who did not. No other donor, recipient, or operative factors were significantly associated with 3-year ECD. CONCLUSIONS AND RELEVANCE Donor diabetes, lower screening ECD, a PACE diagnosis in the recipient, and operative complications were associated with lower ECD at 3 years after DSAEK surgery and may be associated with long-term graft success. While causation cannot be inferred, further studies on the association of donor diabetes and PACE in recipients with lower 3-year ECD warrant further study.

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Involvement of advanced glycation end products, oxidative stress and nuclear factor-kappaB in the development of diabetic keratopathy

Abstract: The higher expression of AGE, 8-OHdG and NF-κB in corneal tissues of diabetic rats suggests that these factors are involved in apoptosis and in subsequent corneal alterations related to diabetic keratopathy.

Cited by 73 publications

References 39 publications

Corneal Changes in Diabetes Mellitus

Corneal Changes in Diabetes Mellitus

Diabetic complications in the cornea

Donor, Recipient, and Operative Factors Associated With Increased Endothelial Cell Loss in the Cornea Preservation Time Study

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