Photoreceptor cell calcium dysregulation and calpain activation promote pathogenic photoreceptor oxidative stress and inflammation in prodromal diabetic retinopathy.

Complications of diabetes mellitus (DM) include diabetic retinopathy (RD) both non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR). The development of RD depends on environmental and genetic factors. MnSOD gene (manganese-superoxid dismutase) is one of the candidate risk factors gene for RD. The presence of V16A MnSOD gene polymorphism results in decrease of mitochondrial MnSOD enzymes expression and triggers the oxidative stress. Hyperglycemia in DM increases oxidative stress in tissues, including the retina resulting in metabolic abnormalities in the retina, which play a role in the development of DM complications, namely diabetic retinopathy. In Indonesia, especially the Javanese tribes in Yogyakarta, there has never been any research on MnSOD gene polymorphism in type 2 diabetes patients with and without retinopathy. Subjects were Poly Endocrine patients and Eye Polyclinic patients of Dr. Sardjito’s General Hospital, 121 subjects consisting of 63 type 2 DM patients without retinopathy were group 1 (KI) and 58 type 2 DM patients with retinopathy were group 2 (KII) (20 NPDR subjects and 38 PDR subjects). V16A polymorphism of MnSOD gene from leukocytes DNA was analyzed by PCR-RFLP method. From 121 DM subjects, 70 subjects with VV genotype were found, 50 subjects with VA genotype and 1 subject with AA genotype. From 63 non-RD DM subjects, 22 subjects with VA genotypes and 41 subjects with VV genotype were found, while in DM with retinopathy (non-PDR, n = 20) found 6 subjects with VA genotype and 14 subjects with VV genotype, and in DM with retinopathy (PDR, n = 38) found 1 subject with AA genotype, 22 subjects with VA genotype and 15 subjects with VV genotype. In DM with retinopathy (NPDR and PDR, n = 58), 1 subject was found with AA genotype, 27 subjects with VA genotype and 29 subjects with VV genotype.

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Notoginsenoside R1 Ameliorates Diabetic Retinopathy through PINK1-Dependent Activation of Mitophagy

Cells ◽

10.3390/cells8030213 ◽

2019 ◽

Vol 8 (3) ◽

pp. 213 ◽

Cited By ~ 15

Author(s):

Ping Zhou ◽

Weijie Xie ◽

Xiangbao Meng ◽

Yadong Zhai ◽

Xi Dong ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetic Retinopathy ◽

Oral Treatment ◽

Müller Cells ◽

Panax Notoginseng ◽

Protective Effects ◽

Muller Cells ◽

Beneficial Effects ◽

Pre Treatment ◽

Lc3 Puncta

: Accumulating evidence has indicated that inflammation, oxidative stress, apoptosis, and autophagy in retinal Müller cells are involved in diabetic retinopathy (DR). Notoginsenoside R1 (NGR1), a novel saponin extracted from Panax notoginseng, posesses pharmacological properties, including treating diabetic encephalopathy and improving microcirculatory disorders. Nevertheless, its beneficial effects on DR and the potential mechanism remain to be elucidated. In this study, we found retinal vascular degeneration, reduced retinal thickness, and impaired retinal function in db/db mice were all dramatically attenuated by oral treatment with NGR1 (30 mg/kg) for 12 weeks. NGR1 pretreatment also significantly inhibited apoptosis, markedly suppressed the VEGF expression, markedly increased PEDF expression and markedly inhibited oxidative stress and inflammation in rat retinal Müller cells (rMC-1) subjected to high glucose (HG) and in the retinas of db/db mice. Furthermore, NGR1 pre-treatment upregulated the level of PINK1 and Parkin, increased the LC3-II/LC3-I ratio, and downregulated the level of p62/SQSTM1 in rMC-1 cells induced by HG and in the retinas of db/db mice. Moreover, NGR1 administration enhanced the co-localization of GFP-LC3 puncta and MitoTracker in rMC-1 cells. Importantly, knockdown of PINK1 abolished the protective effects of NGR1. In conclusion, these phenomena suggested that NGR1 prevented DR via PINK1-dependent enhancement of mitophagy.

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Oxidative stress modulates rearrangement of endoplasmic reticulum-mitochondria contacts and calcium dysregulation in a Friedreich's ataxia model

Redox Biology ◽

10.1016/j.redox.2020.101762 ◽

2020 ◽

Vol 37 ◽

pp. 101762

Author(s):

Laura R. Rodríguez ◽

Pablo Calap-Quintana ◽

Tamara Lapeña-Luzón ◽

Federico V. Pallardó ◽

Stephan Schneuwly ◽

...

Keyword(s):

Oxidative Stress ◽

Endoplasmic Reticulum ◽

Friedreich’S Ataxia ◽

Friedreich's Ataxia ◽

Calcium Dysregulation

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Role of Oxidative Stress in Diabetic Retinopathy and the Beneficial Effects of Flavonoids

Current Pharmaceutical Design ◽

10.2174/1381612824666180515151043 ◽

2018 ◽

Vol 24 (19) ◽

pp. 2180-2187 ◽

Cited By ~ 7

Author(s):

Mohammad Shamsul Ola ◽

Dalia Al-Dosari ◽

Abdullah S. Alhomida

Keyword(s):

Oxidative Stress ◽

Diabetic Retinopathy ◽

Experimental Studies ◽

Developed Countries ◽

Retinal Damage ◽

Beneficial Effects ◽

Diabetic Retina ◽

Retinal Pathology ◽

Dietary Flavonoids

Diabetic Retinopathy (DR) is one of the leading causes of decreased vision and blindness in developed countries. Diabetes-induced metabolic disorder is believed to increase oxidative stress in the retina. This results in deleterious change through dysregulation of cellular physiology that damages both neuronal and vascular cells. In this review, we first highlight the evidence of potential metabolic sources and pathways which increase oxidative stress that contribute to retinal pathology in diabetes. As oxidative stress is a central factor in the pathophysiology of DR, antioxidants therapy would be beneficial towards preventing the retinal damage. A number of experimental studies by our group and others showed that dietary flavonoids cause reduction in increased oxidative stress and other beneficial effects in diabetic retina. We then discuss the beneficial effects of the six major flavonoid families, such as flavanones, flavanols, flavonols, isoflavones, flavones and anthocyanins, which have been studied to improve retinal damage. Flavanoids, being known antioxidants, may ameliorate the retinal degenerative factors including apoptosis, inflammation and neurodegeneration in diabetes. Therefore, intake of potential dietary flavonoids would limit oxidative stress and thereby prevent the retinal damage, and subsequently the development of DR.

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