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Oxidative stress and diabetic retinopathy: development and treatment.

ABSTRACT: Diabetic retinopathy (DR) is the most common microvascular complication in diabetic patients and one of the main causes of acquired blindness in the world. From the 90s until date, the incidence of this complication has increased. Reactive oxygen species (ROS) is a free radical with impaired electron that usually participates in the redox mechanisms of some body molecules such as enzymes, proteins, and so on. In normal biological conditions, ROS is maintained in equilibrium, however its overproduction can lead to biological process called oxidative stress and this is considered the main pathogenesis of DR. The retina is susceptible to ROS because of high-energy demands and exposure to light. When the balance is broken, ROS produces retinal cell injury by interacting with the cellular components. This article describes the possible role of oxidative stress in the development of DR and proposes some treatment options based on its stages. The review of the topic shows that blindness caused by DR can be avoided by early detection and timely treatment.

SUBMITTER: Calderon GD

PROVIDER: S-EPMC5558229 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Oxidative stress and diabetic retinopathy: development and treatment.

Calderon G D GD Juarez O H OH Hernandez G E GE Punzo S M SM De la Cruz Z D ZD

Eye (London, England) 20170428 8

Diabetic retinopathy (DR) is the most common microvascular complication in diabetic patients and one of the main causes of acquired blindness in the world. From the 90s until date, the incidence of this complication has increased. Reactive oxygen species (ROS) is a free radical with impaired electron that usually participates in the redox mechanisms of some body molecules such as enzymes, proteins, and so on. In normal biological conditions, ROS is maintained in equilibrium, however its overprod ...[more]

PMID: 28452994

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Project description:PurposeDiabetic retinopathy (DR) is one of the most common reasons for blindness. uncoupling protein 2 (UCP2), an uncoupling protein located in mitochondria, has been reported to be related to metabolic and vascular diseases. This research aimed to illustrate the function and mechanism of UCP2 in the pathogenesis of DR.MethodsHuman epiretinal membranes were collected to investigate the expression of UCP2 by quantitative real-time polymerase chain reaction (qRT-PCR) and immunofluorescence. Primary human retinal microvascular endothelial cells (HRECs) were cultured in high glucose (HG) to establish an in vitro cell model for DR. Flow cytometry analysis was used to measure intracellular reactive oxygen species (ROS). Senescence levels were evaluated by the senescence-associated beta-galactosidase (SA-β-gal) assay, the expression of senescence marker P21, and cell-cycle analysis. Adenovirus-mediated UCP2 overexpression or knockdown and specific inhibitors were administered to investigate the underlying regulatory mechanism.ResultsProliferative fibrovascular membranes from patients with DR illustrated the downregulation of UCP2 and sirtuin 3 (SIRT3) by qRT-PCR and immunofluorescence. Persistent hyperglycemia-induced UCP2 downregulation in the progress of DR and adenovirus-mediated UCP2 overexpression protected endothelial cells from hyperglycemia-induced oxidative stress and senescence. Under hyperglycemic conditions, UCP2 overexpression attenuated NAD+ downregulation; hence, it promoted the expression and activity of SIRT3, an NAD+-dependent deacetylase regulating mitochondrial function. 3-TYP, a selective SIRT3 inhibitor, abolished the UCP2-mediated protective effect against oxidative stress and senescence.ConclusionsUCP2 overexpression relieved oxidative stress and senescence based on a novel mechanism whereby UCP2 can regulate the NAD+-SIRT3 axis. Targeting oxidative stress and senescence amelioration, UCP2-SIRT3 signaling may serve as a method for the prevention and treatment of DR and other diabetic vascular diseases.

Dataset Information

Oxidative stress and diabetic retinopathy: development and treatment.

Publications

Oxidative stress and diabetic retinopathy: development and treatment.

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