Advanced Glycation End Products and Ultrastructural Changes in Corneas of Long-term Streptozotocin-Induced Diabetic Monkeys

Zou, Chunlin; Wang, Shuyan; Huang, Fen; Zhang, Yu A.

doi:10.1097/ico.0b013e3182490907

Cited by 31 publications

(21 citation statements)

References 10 publications

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“…The lack of pentosidine was reported also in a recent study on crosslinks in adult human corneas [39]. In other studies, no immunoreactivity to different types of AGEs was detected in normal human corneas in adults of different age [40] and in healthy corneas in monkeys [41]. As concerns thermal denaturation of cornea, very little literature exists [27,39] and the only one reporting age-related changes [39] shows rather a slight decrease in denaturation temperature without any signs of age-related corneal crosslinking.…”

Section: Discussionsupporting

confidence: 54%

Thermal stability of collagen in naturally ageing and in vitro glycated rabbit tissues

Trębacz

Szczęsna

Arczewska

2018

J Therm Anal Calorim

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The aim of the work was to compare glycation-related changes in thermal denaturation of collagen in naturally ageing and in vitro ribosylated tissues. Samples of cornea, meniscus and Achilles tendon from young adult and from ageing rabbits were compared. Moreover, in vitro glycated samples (ribose, 100 mg mL -1 , 14 days) were prepared for both age groups. Collagen in tissues was characterized in terms of thermal denaturation parameters obtained from differential scanning calorimetry. The level of pentosidine and other fluorescent advanced glycation end products (AGEs) in the papain-digested tissue samples was evaluated using spectrofluorimetry (k ex/em : 335/385 and 370/440 nm). In naturally ageing tissues, changes in properties of extracellular matrix collagen expressed in terms of parameters of thermal denaturation and fluorescent AGEs levels were tissue dependent and were related to differences in organization of matrix components. No signs of increased level of AGEs were found in the naturally ageing cornea, unlike in the tendon and meniscus. In vitro ribation proved by gains of fluorescent AGEs affected thermal stability of collagen in all tissues, both in young adult and in the ageing ones. The effects of ribation were considerably greater than the effects of natural ageing. The increase in denaturation temperature was similarly strong in all tissues and did not correlate with the increase in fluorescent AGEs. As a conclusion, parameters of collagen thermal denaturation are tissue and age dependent and an amount of fluorescent AGEs is not the only determinant of increasing thermal stability of glycated collagen.

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Section: Discussionsupporting

confidence: 54%

Thermal stability of collagen in naturally ageing and in vitro glycated rabbit tissues

Trębacz

Szczęsna

Arczewska

2018

J Therm Anal Calorim

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“…In patients with NIDDM corneal stroma acquires abnormal collagen fibril bundles of variable thickness (Rehany et al, 2000b). In monkeys with induced IDDM similar stromal bundles were found (Zou et al, 2012). 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).…”

Section: General Manifestations Of Diabetes In the Corneamentioning

confidence: 52%

“…Corneal diabetic alterations include increased central thickness, altered BM composition, abnormal collagen structure in the stroma and accumulation of AGEs that may cause collagen crosslinking (Ljubimov et al, 1998; Rehany et al, 2000b; Zou et al, 2012; El-Agamy and Alsubaie, 2017). Therefore, corneal biomechanics may be also altered in diabetics.…”

Section: General Manifestations Of Diabetes In the Corneamentioning

confidence: 99%

“…Hyperglycemia in diabetics causes non-enzymatic glycosylation of proteins leading to the formation of AGEs that accumulate in diabetic tissues (Zou et al, 2012; Madonna et al, 2017). 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).…”

Section: Molecular Alterations and Disease Markers Of Diabetes In mentioning

confidence: 99%

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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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“…Thus, on one hand, in view of this distinct pathophysiological background, the lack of close correlations between measures of CCM and peripheral nerve tests may not be surprising. On the other hand, advanced glycation end-product immunoreactivity was observed in epithelial cells, epithelial basement membrane, and stromal keratocytes in corneas from diabetic monkeys (40), suggesting that one possible mechanism for the development of corneal neuropathy could be nonenzymatic glycation, similar to its putative role in the pathogenesis of DSPN (36).…”

Section: Discussionmentioning

confidence: 99%

Early Detection of Nerve Fiber Loss by Corneal Confocal Microscopy and Skin Biopsy in Recently Diagnosed Type 2 Diabetes

et al. 2014

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We sought to determine whether early nerve damage may be detected by corneal confocal microscopy (CCM), skin biopsy, and neurophysiological tests in 86 recently diagnosed type 2 diabetic patients compared with 48 control subjects. CCM analysis using novel algorithms to reconstruct nerve fiber images was performed for all fibers and major nerve fibers (MNF) only. Intraepidermal nerve fiber density (IENFD) was assessed in skin specimens. Neurophysiological measures included nerve conduction studies (NCS), quantitative sensory testing (QST), and cardiovascular autonomic function tests (AFTs). Compared with control subjects, diabetic patients exhibited significantly reduced corneal nerve fiber length (CNFL-MNF), fiber density (CNFD-MNF), branch density (CNBD-MNF), connecting points (CNCP), IENFD, NCS, QST, and AFTs. CNFD-MNF and IENFD were reduced below the 2.5th percentile in 21% and 14% of the diabetic patients, respectively. However, the vast majority of patients with abnormal CNFD showed concomitantly normal IENFD and vice versa. In conclusion, CCM and skin biopsy both detect nerve fiber loss in recently diagnosed type 2 diabetes, but largely in different patients, suggesting a patchy manifestation pattern of small fiber neuropathy. Concomitant NCS impairment points to an early parallel involvement of small and large fibers, but the precise temporal sequence should be clarified in prospective studies.

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Advanced Glycation End Products and Ultrastructural Changes in Corneas of Long-term Streptozotocin-Induced Diabetic Monkeys

Abstract: Abnormal aggregates of collagen fibrils in stromal matrix were common among long-term diabetic monkeys, and the formation of the abnormal collagen fibril aggregates might result from excessive nonenzymatic glycosylation.

Cited by 31 publications

References 10 publications

Thermal stability of collagen in naturally ageing and in vitro glycated rabbit tissues

Thermal stability of collagen in naturally ageing and in vitro glycated rabbit tissues

Diabetic complications in the cornea

Early Detection of Nerve Fiber Loss by Corneal Confocal Microscopy and Skin Biopsy in Recently Diagnosed Type 2 Diabetes

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