Advanced glycation end products induce death of retinal neurons via activation of nitric oxide synthase

Kobayashi, Takatoshi; Oku, Hidehiro; Komori, Asako; Okuno, Takashi; Kojima, Shota; Obayashi, Hiroshi; Sugiyama, Tetsuya; Hasegawa, Goji; Fukui, Michiaki; Nakamura, Naoto; Ikeda, Tsunehiko

doi:10.1016/j.exer.2005.04.001

Cited by 16 publications

(5 citation statements)

References 38 publications

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“…Therefore, the increased availability of NO by supplementation of L-arginine and sepiapterin with inhibition by the uncoupling of eNOS could result in the reduced generation of superoxide. Our results are consistent with previous studies that found that AGE enhanced peroxynitrite formation mediated by NO and superoxide in retinal neurons [58,61,62]. Various reactive oxygen species other than superoxide are formed by AGE and this could lead to oxidative stress unrelated to NO or superoxide.…”

Section: Discussionsupporting

confidence: 93%

Effect of Advanced Glycation End Products on Oxidative Stress and Senescence of Trabecular Meshwork Cells

Park

Kim

2012

Korean J Ophthalmol

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PurposeTo investigate the effect of advanced glycation end products (AGE) on oxidative stress and cellular senescence in cultured human trabecular meshwork cells (HTMC).MethodsPrimarily cultured HTMC were exposed to 0, 10, 50, 100, 200 µg/mL of glycated bovine serum albumin (G-BSA) for 5 days. Also co-exposed were L-arginine, sepiapterin, and antioxidant N-acetylcysteine (NAC). Cellular survival and production of nitric oxide (NO), superoxide, and reactive oxygen species were assessed by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide assay, Griess assay, cytochrome c assay, and dichlorofluorescin diacetate assay, respectively. Senescence-associated β-galactosidase staining was performed to quantify the degree of cellular senescence.ResultsG-BSA decreased cellular survival, NO production, and increased superoxide production significantly in a dose-dependent manner. The effects of G-BSA were abolished with co-exposure of L-arginine, sepiapterin, and NAC. G-BSA enhanced cellular senescence accompanied by increased production of reactive oxygen species. G-BSA-induced cellular senescence was suppressed by application of L-arginine, sepiapterin, and NAC.ConclusionsAGE enhances cellular senescence of HTMC accompanied with increased oxidative stress. AGE-induced oxidative stress and cellular senescence could be delayed by application of anti-oxidants.

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Section: Discussionsupporting

confidence: 93%

Effect of Advanced Glycation End Products on Oxidative Stress and Senescence of Trabecular Meshwork Cells

Park

Kim

2012

Korean J Ophthalmol

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“…In vitro , retinal neuronal cell death induced by AGEs and hyperglycemia has been shown to occur in a time- and dose-dependent manner and be mediated through the activation of ROS, suggesting oxidative stress is a consequence of AGEs/RAGE interaction [78]. Both AGEs and ROS have been demonstrated to induce retinal ganglion cell degeneration, possibly mediated by PI3 kinase-dependent pathways [75].…”

Section: The Pathogenesis Of Diabetic Macular Edemamentioning

confidence: 99%

Diabetic macular edema: new concepts in patho-physiology and treatment

et al. 2014

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Diabetic macular edema (DME), a serious eye complication caused primarily by hyperglycemia, is one of the major causes of blindness. DME, which is characterized by cystic retinal thickening or lipid deposition, is prone to relapse after successful treatment. DME is a complex pathological process caused by multiple factors, including breakdown of the inner and outer blood-retinal barriers, oxidative stress, and elevated levels of vascular endothelial growth factor which have been demonstrated in both preclinical and clinical studies. Starling’s law theory explains many of the features of DME. Early detection and treatment of DME can prevent vision loss. Current effective interventions for DME include treatment of systemic risk factors, such as elevated blood glucose, blood pressure and dyslipidemia. Ophthalmic treatments include laser photocoagulation, surgery and intraocular pharmacotherapy. New drugs, which are given by intraocular injection, have emerged in recent years to become first line treatment for DME that affects the central macula with loss of vision. Laser photocoagulation is still the gold standard of treatment for DME which does not involve the central macular. This review outlines these new treatments with particular emphasis on the optimal timing of how they are given.

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“…Finally, this pathway has been demonstrated to lead to oxidative stress and trigger proinflammatory signaling, implicated in endothelial dysfunction, arterial stiffening, and microvascular complications [ 121 – 123 ]. Studies in vitro have analyzed the effects of AGEs on the retinal neuronal population, evidencing a depressing influence on the neuritic regeneration [ 124 ] and a stimulated proapoptotic trend [ 34 , 125 – 127 ]. In addition, they showed AGEs effects on Müller glia.…”

Section: Mechanisms Of Diabetic Milieu -Mediatementioning

confidence: 99%

Primary Retinal Cultures as a Tool for Modeling Diabetic Retinopathy: An Overview

Matteucci

Varano

Mallozzi

et al. 2015

BioMed Research International

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Experimental models of diabetic retinopathy (DR) have had a crucial role in the comprehension of the pathophysiology of the disease and the identification of new therapeutic strategies. Most of these studies have been conducted in vivo, in animal models. However, a significant contribution has also been provided by studies on retinal cultures, especially regarding the effects of the potentially toxic components of the diabetic milieu on retinal cell homeostasis, the characterization of the mechanisms on the basis of retinal damage, and the identification of potentially protective molecules. In this review, we highlight the contribution given by primary retinal cultures to the study of DR, focusing on early neuroglial impairment. We also speculate on possible themes into which studies based on retinal cell cultures could provide deeper insight.

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Advanced glycation end products induce death of retinal neurons via activation of nitric oxide synthase

Cited by 16 publications

References 38 publications

Effect of Advanced Glycation End Products on Oxidative Stress and Senescence of Trabecular Meshwork Cells

Effect of Advanced Glycation End Products on Oxidative Stress and Senescence of Trabecular Meshwork Cells

Diabetic macular edema: new concepts in patho-physiology and treatment

Primary Retinal Cultures as a Tool for Modeling Diabetic Retinopathy: An Overview

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