Corneal Sensitivity Is Reduced and Relates to the Severity of Neuropathy in Patients With Diabetes

Tavakoli, Mitra; Kallinikos, Panagiotis A.; Efron, Nathan; Boulton, Andrew J.M.; Malik, Rayaz A.

doi:10.2337/dc07-0175

Cited by 123 publications

(118 citation statements)

References 24 publications

(29 reference statements)

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“…In diabetes, corneal sensitivity, nerve fiber density, and epithelial wound healing are reduced significantly (27,31,32). However, the mechanisms are not completely understood.…”

Section: Discussionmentioning

confidence: 99%

“…Corneal nerve fibers exert important trophic influences and contribute to the maintenance of corneal epithelium homeostasis, whereas the dysfunction of corneal innervation produces an impairment of corneal epithelial wound healing, known as neurotrophic keratitis, as caused by for instance herpetic viral infections, trigeminal nerve damage, or diabetes (27)(28)(29). Although tear fluid impairment is also involved (30), the neurotrophic deficits may play a major role in the pathogenesis of diabetic keratopathy, as the density of corneal nerve fibers and corneal sensation decreased in diabetic patients (31)(32)(33). However, although being the major sensory neurotransmitter and neuropeptide released from corneal nerve fibers, SP was shown not to be significantly decreased in diabetic cornea (34).…”

mentioning

confidence: 99%

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Substance P Promotes Diabetic Corneal Epithelial Wound Healing Through Molecular Mechanisms Mediated via the Neurokinin-1 Receptor

et al. 2014

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Substance P (SP) is a neuropeptide, predominantly released from sensory nerve fibers, with a potentially protective role in diabetic corneal epithelial wound healing. However, the molecular mechanism remains unclear. We investigated the protective mechanism of SP against hyperglycemia-induced corneal epithelial wound healing defects, using type 1 diabetic mice and high glucose–treated corneal epithelial cells. Hyperglycemia induced delayed corneal epithelial wound healing, accompanied by attenuated corneal sensation, mitochondrial dysfunction, and impairments of Akt, epidermal growth factor receptor (EGFR), and Sirt1 activation, as well as decreased reactive oxygen species (ROS) scavenging capacity. However, SP application promoted epithelial wound healing, recovery of corneal sensation, improvement of mitochondrial function, and reactivation of Akt, EGFR, and Sirt1, as well as increased ROS scavenging capacity, in both diabetic mouse corneal epithelium and high glucose–treated corneal epithelial cells. The promotion of SP on diabetic corneal epithelial healing was completely abolished by a neurokinin-1 (NK-1) receptor antagonist. Moreover, the subconjunctival injection of NK-1 receptor antagonist also caused diabetic corneal pathological changes in normal mice. In conclusion, the results suggest that SP-NK-1 receptor signaling plays a critical role in the maintenance of corneal epithelium homeostasis, and that SP signaling through the NK-1 receptor contributes to the promotion of diabetic corneal epithelial wound healing by rescued activation of Akt, EGFR, and Sirt1, improvement of mitochondrial function, and increased ROS scavenging capacity.

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“…In diabetes, corneal sensitivity, nerve fiber density, and epithelial wound healing are reduced significantly (27,31,32). However, the mechanisms are not completely understood.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Substance P Promotes Diabetic Corneal Epithelial Wound Healing Through Molecular Mechanisms Mediated via the Neurokinin-1 Receptor

et al. 2014

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“…Corneal nerve morphology [6] and corneal sensitivity [7] have both recently demonstrated promising relationships with established clinical measures of DPN. Optical coherence tomography (OCT) has enabled high resolution, non-invasive imaging of the complex neural networks within the retina.…”

Section: Introductionmentioning

confidence: 99%

Visual sensitivity loss in the central 30° of visual field is associated with diabetic peripheral neuropathy

et al. 2012

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“…Нервные волокна в области лимба теряют свою миелиновую оболочку и далее следуют в окружении шванновских клеток, меняя пространственную ориентацию и образуя суббазальное нервное сплетение между базальным эпителием роговицы и боуменовой мембраной. Ме-тод конфокальной микроскопии позволяет полу-чать качественные изображения суббазального нервного сплетения центральной части роговицы и оценивать плотность нервных волокон роговицы на 1 мм 2 (NFD), длину нервных волокон на 1 мм 2 (NFL); плотность нервных ветвей нервов на 1 мм 2 (NBD), а также их ветвистость (ТС -коэффициент извитости) [32,33]. В исследовании M. Tavakoli и соавт.…”

Section: эволюция методов диагностики нарушений периферической нервноunclassified

Confocal retinal microscopy - the new non-invasive method for diagnostics of the early manifestations of the lesions in the peripheral nervous system associated with diabetes mellitus

Artemova¹,

Галстян²,

Атарщиков³

et al. 2015

Probl Endokrinol (Mosk)

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ОБЗОРЫДиабетическая полинейропатия (ДПН) являет-ся одним из наиболее распространенных поздних осложнений сахарного диабета (СД), а также глав-ной причиной язвенных дефектов стоп [1]. В связи с неуклонным ростом заболеваемости СД 2-го типа проблема приобретает все большие масштабы [2]. По современным представлениям, распространен-ность нейропатии на стадии явных клинических симптомов может достигать 21,9% [3], тогда как не-врологический дефицит уже имеют около 50% па-циентов с СД [4]. Недавно показано, что распро-страненность нейропатии среди лиц с СД составля-ет около 28%, однако начальные признаки повреж-дения периферической нервной системы обнаружи-вались уже у 13% пациентов с нарушением толе-рантности к глюкозе (НТГ) [5]. Различия в частоте встречаемости ДПН обусловлены отсутствием на-дежных методов диагностики, а также использова-нием различных критериев оценки степени тяжести нейропатии. Вероятно, повреждение нервных воло-кон может предшествовать развитию других ослож-нений СД и в ряде случаев быть первым клиниче-ским признаком нарушения углеводного обмена. There are presently no reliable methods for diagnostics of the early manifestations of the lesions in the peripheral nervous system. Only puncture biopsy of the skin and the nerves can be used at the preclinical stage. However, the application of these invasive methods is fraught with the risk of infectious complications. Confocal retinal microscopy is the new non-invasive morphometric technique that permits to reveal the early signs of the lesions in the peripheral nervous system and to study dynamics of the associated changes that can be used as a valid surrogate end point for the evaluation of the effectiveness of pharmacotherapy.

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Corneal Sensitivity Is Reduced and Relates to the Severity of Neuropathy in Patients With Diabetes

Cited by 123 publications

References 24 publications

Substance P Promotes Diabetic Corneal Epithelial Wound Healing Through Molecular Mechanisms Mediated via the Neurokinin-1 Receptor

Substance P Promotes Diabetic Corneal Epithelial Wound Healing Through Molecular Mechanisms Mediated via the Neurokinin-1 Receptor

Visual sensitivity loss in the central 30° of visual field is associated with diabetic peripheral neuropathy

Confocal retinal microscopy - the new non-invasive method for diagnostics of the early manifestations of the lesions in the peripheral nervous system associated with diabetes mellitus

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