TheUCP1−3826A/G Polymorphism Is Associated with Diabetic Retinopathy and IncreasedUCP1andMnSOD2Gene Expression in Human Retina

Brondani, Letícia A.; Souza, Bianca Marmontel de; Duarte, Guilherme Coutinho Kullmann; Kliemann, Lúcia Maria; Esteves, J; Marcon, Alexandre S.; Gross, Jorge Luiz; Canani, Luís Henrique Santos; Crispim, Daisy

doi:10.1167/iovs.12-10660

Cited by 35 publications

(37 citation statements)

References 43 publications

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“…Recent studies have shown an association between UCP1 -3826A/G polymorphism and retinopathy in type I diabetic patients [64]. However, the exact role of UCPs in mitochondrial homeostasis in the development of diabetic retinopathy remains to be explored.…”

Section: Mitochondrial Damagementioning

confidence: 99%

Oxidative stress, mitochondrial damage and diabetic retinopathy

Kowluru

Mishra

2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

262

232

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Diabetes has emerged as an epidemic of the 21st century, and retinopathy remains the leading cause of blindness in young adults and the mechanism of this blinding disease remains evasive. Diabetes-induced metabolic abnormalities have been identified, but a causal relationship between any specific abnormality and the development of this multi-factorial disease is unclear. Reactive oxygen species (ROS) are increased and the antioxidant defense system is compromised. Increased ROS result in retinal metabolic abnormalities, and these metabolic abnormalities can also produce ROS. Sustained exposure to ROS damages the mitochondria and compromises the electron transport system (ETC), and, ultimately, the mitochondrial DNA (mtDNA) is damaged. Damaged mtDNA impairs its transcription, and the vicious cycle of ROS continues to propagate. Many genes important in generation and neutralization of ROS are also epigenetically modified further increasing ROS, and the futile cycle continues to fuel in. Antioxidants have generated beneficial effects in ameliorating retinopathy in diabetic rodents, but limited clinical studies have not been encouraging. With the ongoing use of antioxidants for other chronic diseases, there is a need for a controlled trial to recognize their potential in ameliorating the development of this devastating disease.

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Section: Mitochondrial Damagementioning

confidence: 99%

Oxidative stress, mitochondrial damage and diabetic retinopathy

Kowluru

Mishra

2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

262

232

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“…27 A polymorphism in the -3826A/G allele of uncoupling protein (UCP)-1 has also been reported to diminish UCP-1's protective effects against ROS, thus increasing oxidative stress in diabetic patients. 28 In addition, 866G/A, Ala55Val, and 45-bp insertion/deletion polymorphisms in UCP-2 genes have been associated with the promotion of DR by also decreasing UCP-2's protective effects against ROS. 29 …”

Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

Mechanistic Insights into Pathological Changes in the Diabetic Retina

Roy

Kern

Song

et al. 2017

The American Journal of Pathology

161

130

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Increasing evidence points to inflammation as one of the key players in diabetes-mediating adverse effects to the neuronal and vascular components of the retina. Sustained inflammation induces biochemical and molecular changes, ultimately contributing to retinal complications and vision loss in diabetic retinopathy. In this review, we describe changes involving metabolic abnormalities secondary to hyperglycemia, oxidative stress, and activation of transcription factors, together with neuroglial alterations in the diabetic retina. Changes in biochemical pathways and how they promote pathophysiologic developments involving proinflammatory cytokines, chemokines, and adhesion molecules are discussed. Inflammation-mediated leukostasis, retinal ischemia, and neovascularization and their contribution to pathological and clinical stages leading to vision loss in diabetic retinopathy (DR) are highlighted. In addition, potential treatment strategies involving fibrates, connexins, neuroprotectants, photobiomodulation, and anti-inflammatory agents against the development and progression of DR lesions are reviewed. The importance of appropriate animal models for testing novel strategies against DR lesions is discussed; in particular, a novel nonhuman primate model of DR and the suitability of rodent models are weighed. The purpose of this review is to highlight our current understanding of the pathogenesis of DR and to summarize recent advances using novel approaches or targets to investigate and inhibit the retinopathy. (Am J Pathol 2017, 187: 9e19; http://dx

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“…Slides were incubated with primary antibody and then with a biotinylated secondary antibody, streptavidinYhorseradish peroxidase conjugate (LSAB; Dako Cytomation, Inc., Carpinteria, CA), and diaminobenzidine tetrahydrochloride (kit DAB; Dako Cytomation, Inc.). Quantifications of TNF, IL-6, IL-1A, IFN-F, and TF proteins were performed by digital image analyses using Image Pro Plus software, version 4.5 (Media Cybernetics, Bethesda, MD) (49). Images were visualized through a Zeiss microscope (model AXIOSKOP-40; Carl Zeiss, Oberkochen, Germany) and captured using the Cool Snap-Pro CS (Media Cybernetics) camera in a blinded fashion.…”

Section: Brain-dead Patients and Controlsmentioning

confidence: 99%