Update on the Effects of Antioxidants on Diabetic Retinopathy: In Vitro Experiments, Animal Studies and Clinical Trials

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Abstract

Current therapies for diabetic retinopathy (DR) incorporate blood glucose and blood pressure control, vitrectomy, photocoagulation, and intravitreal injections of anti-vascular endothelial growth factors or corticosteroids. Nonetheless, these techniques have not been demonstrated to completely stop the evolution of this disorder. The pathophysiology of DR is not fully known, but there is more and more evidence indicating that oxidative stress is an important mechanism in the progression of DR. In this sense, antioxidants have been suggested as a possible therapy to reduce the complications of DR. In this review we aim to assemble updated information in relation to in vitro experiments, animal studies and clinical trials dealing with the effect of the antioxidants on DR.

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Effect of long-term administration of alpha-lipoic acid on retinal capillary cell death and the development of retinopathy in diabetic rats.

Sarah Odenbach, Renu A Kowluru (2004)

Oxidative stress is increased in the retina in diabetes, and it is considered to play an important role in the development of retinopathy. alpha-Lipoic acid, a thiol antioxidant, has been shown to have beneficial effects on polyneuropathy and on the parameters of oxidative stress in various tissues, including nerve, kidney, and retina. The purpose of this study was to examine the effect of alpha-lipoic acid on retinal capillary cell apoptosis and the development of pathology in diabetes. Retina was used from streptozotocin-induced diabetic rats receiving diets supplemented with or without alpha-lipoic acid (400 mg/kg) for 11 months of diabetes. Capillary cell apoptosis (by terminal transferase-mediated dUTP nick-end labeling) and formation of acellular capillaries were investigated in the trypsin-digested retinal microvessels. The effect of alpha-lipoic acid administration on retinal 8-hydroxy-2'deoxyguanosine (8-OHdG) and nitrotyrosine levels was determined by enzyme-linked immunosorbent assay. alpha-Lipoic acid administration for the entire duration of diabetes inhibited capillary cell apoptosis and the number of acellular capillaries in the retina, despite similar severity of hyperglycemia in the two diabetic groups (with and without alpha-lipoic acid). Retinal 8-OHdG and nitrotyrosine levels were increased by over twofold and 70%, respectively, in diabetes, and alpha-lipoic acid administration inhibited these increases. Our results demonstrate that the long-term administration of alpha-lipoic acid has beneficial effects on the development of diabetic retinopathy via inhibition of accumulation of oxidatively modified DNA and nitrotyrosine in the retina. alpha-Lipoic acid supplementation represents an achievable adjunct therapy to help prevent vision loss in diabetic patients.

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Oxidative Stress-Related Mechanisms and Antioxidant Therapy in Diabetic Retinopathy

Cheng-Cheng Li, Xiao Miao, FENGSHENG LI … (2017)

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes and is the leading cause of blindness in young adults. Oxidative stress has been implicated as a critical cause of DR. Metabolic abnormalities induced by high-glucose levels are involved in the development of DR and appear to be influenced by oxidative stress. The imbalance between reactive oxygen species (ROS) production and the antioxidant defense system activates several oxidative stress-related mechanisms that promote the pathogenesis of DR. The damage caused by oxidative stress persists for a considerable time, even after the blood glucose concentration has returned to a normal level. Animal experiments have proved that the use of antioxidants is a beneficial therapeutic strategy for the treatment of DR, but more data are required from clinical trials. The aims of this review are to highlight the improvements to our understanding of the oxidative stress-related mechanisms underlying the development of DR and provide a summary of the main antioxidant therapy strategies used to treat the disease.

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Resveratrol and Ophthalmic Diseases

Khaled Abu-Amero, Altaf A. Kondkar, Kakarla Chalam (2016)

Resveratrol, a naturally occurring plant polyphenol found in grapes, is the principal biologically active component in red wine. Clinical studies have shown that resveratrol due to its potent anti-oxidant and anti-inflammatory properties are cardio-protective, chemotherapeutic, neuroprotective, and display anti-aging effects. Oxidative stress and inflammation play a critical role in the initiation and progression of age-related ocular diseases (glaucoma, cataract, diabetic retinopathy and macular degeneration) that lead to progressive loss of vision and blindness. In vitro and in vivo (animal model) experimental studies performed so far have provided evidence for the biological effects of resveratrol on numerous pathways including oxidative stress, inflammation, mitochondrial dysfunction, apoptosis, pro-survival or angiogenesis that are implicated in the pathogenesis of these age-related ocular disorders. In this review, we provide a brief overview of current scientific literature on resveratrol, its plausible mechanism(s) of action, its potential use and current limitations as a nutritional therapeutic intervention in the eye and its related disorders.

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Journal

Journal ID (nlm-ta): Antioxidants (Basel)

Journal ID (iso-abbrev): Antioxidants (Basel)

Journal ID (publisher-id): antioxidants

Title: Antioxidants

Publisher: MDPI

ISSN (Electronic): 2076-3921

Publication date (Electronic): 26 June 2020

Publication date Collection: June 2020

Volume: 9

Issue: 6

Electronic Location Identifier: 561

Affiliations

[1 ]Department of Ophthalmology, General University Hospital Morales Meseguer, 30007 Murcia, Spain; elena.rubio@ 123456carm.es (E.R.-V.); elisam.foulquie@ 123456carm.es (E.F.-M.)

[2 ]Department of Ophthalmology and Optometry, University of Murcia, 30120 Murcia, Spain

[3 ]Ophthalmic Research Unit Santiago Grisolia, 46017 Valencia, Spain

[4 ]Cellular and Molecular Ophthalmolobiology Group, Surgery Department of the University of Valencia, 46010 Valencia, Spain

[5 ]Red Temática de Investigación Cooperativa en Patología Ocular (OFTARED), Instituto de Salud Carlos III, 28029 Madrid, Spain; rcasaroli@ 123456ub.edu

[6 ]Department of Surgery & Hospital Clinic de Barcelona (IDIBAPS), School of Medicine, University of Barcelona, E-08036 Barcelona, Spain

[7 ]Institute of Biomedical Research (IIB-Sant Pau—SGR1113), Banc de Sang i Texits (BST), E-08041 Barcelona, Spain

[8 ]Area of Health Sciences, Valencian International University, 46002 Valencia, Spain; vczanon@ 123456universidadviu.com

[9 ]Department of Anaesthesiology, University Hospital Virgen de la Arrixaca, 30120 Murcia, Spain; monica.delrio@ 123456um.es

Author notes

[* ]Correspondence: jj.garciamedina@ 123456um.es (J.J.G.-M.); dolores.pinazo@ 123456uv.es (M.D.P.-D.)

[†]

V.Z.-M. and M.d.-R.-V. shared last authorship as senior authors.

Author information

Jose Javier Garcia-Medina https://orcid.org/0000-0002-6245-7271

Ricardo P Casaroli-Marano https://orcid.org/0000-0003-1812-9323

Maria Dolores Pinazo-Duran https://orcid.org/0000-0002-0118-7837

Vicente Zanon-Moreno https://orcid.org/0000-0003-1179-1592

Article

Publisher ID: antioxidants-09-00561

DOI: 10.3390/antiox9060561

PMC ID: 7346101

PubMed ID: 32604941

SO-VID: d077a2f3-dc2b-4455-82bc-3b26598f0262

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Update on the Effects of Antioxidants on Diabetic Retinopathy: In Vitro Experiments, Animal Studies and Clinical Trials

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Most cited references 124

Effect of long-term administration of alpha-lipoic acid on retinal capillary cell death and the development of retinopathy in diabetic rats.

Oxidative Stress-Related Mechanisms and Antioxidant Therapy in Diabetic Retinopathy

Resveratrol and Ophthalmic Diseases

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