Contribution of epigenetics in diabetic retinopathy

Kowluru, Renu A.; Mishra, Manish

doi:10.1007/s11427-015-4853-0

Cited by 43 publications

(20 citation statements)

References 89 publications

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“…Several lines of studies have shown that miRNAs play a key role in diabetes and its complications, modulating multiple signaling pathways associated with DR [23][24][25]. Previous studies have shown that miR-200b and miR-146a play an essential role in diabetic retinopathy through modulation of VEGF and fibronectin [15,26].…”

Section: Discussionmentioning

confidence: 99%

MiR-20b targets AKT3 and modulates vascular endothelial growth factor-mediated changes in diabetic retinopathy

Qin

Liu

et al. 2016

ABBS

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Diabetic retinopathy (DR) is the leading cause of new-onset blindness. The roles of microRNAs in diabetic retinopathy are largely unknown. The aim of this study is to investigate the role of miR20b in DR. Transfection of miR-20b mimic in high glucose (HG)-treated human retinal endothelial cells (HRECs) increased miR-20b expression and decreased the expression level of VEGF mRNA, while transfection of miR-20b inhibitor in control HRECs reduced the miR-20b expression with a corresponding increase of VEGF mRNA. In vitro functional assay showed that transfection of miR-20b mimic prevented HG-induced increase in transendothelial permeability and tube formation in HRECs. Transfection of miR-20b inhibitor or treatment of VEGF increased transendothelial permeability and tube formation in control HRECs. Luciferase reported assay showed that AKT3 is a target of miR-20b. Transfection of miR-20b mimic prevented the up-regulation of AKT3 induced by HG without changing the protein levels of other isoforms of AKT, and silencing of AKT3 caused decrease of VEGF mRNA and protein levels as well as prevented HG-induced increase in transendothelial permeability and tube formation. Finally, we showed that miR-20b was down-regulated in the retina and retinal endothelial cells in diabetic rats, with a correlated up-regulation of VEGF and AKT3. Intravitreal injection of miR-20b mimic in the diabetic rat significantly increased the miR-20b expression and decreased the expression levels of AKT3 and VEGF in the retina tissues, and intravitreal delivery of AKT3 siRNA in the diabetic rat significantly decreased the expressions of AKT3 and VEGF. Collectively, miR-20b is important for the regulation of VEGF-mediated changes in HRECs and rat retinal tissues under hyperglycemic conditions possibly via targeting AKT3.

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Section: Discussionmentioning

confidence: 99%

MiR-20b targets AKT3 and modulates vascular endothelial growth factor-mediated changes in diabetic retinopathy

Qin

Liu

et al. 2016

ABBS

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“…Recently, proinflammatory lipids, 13 epigenetic and epigenomic modifications, 14 insulin dysregulation, 15 and b-cellulin signaling, 16 which initiate and contribute to DR pathogenesis independently from hyperglycemic condition, have been identified. biochemical pathways and inflammation in diabetic retinopathy (DR) pathogenesis.…”

Section: Mechanisms Implicated In the Pathogenesis Of Drmentioning

confidence: 99%

Mechanistic Insights into Pathological Changes in the Diabetic Retina

Roy

Kern

Song

et al. 2017

The American Journal of Pathology

170

147

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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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“…Changes of tear AMP levels are likely not the cause but rather the consequence of diabetic retinopathy progression, hence, it can be used to develop bedside test for screening purposes. Currently, photographic methods and retinal image analysis to track neovascularization and increased vascular permeability in the retina can be used for screening [189][190][191], this, however, requires proper instruments, software, and well-trained human graders, making diagnosis available only in big screening centers. In order to make the screening widely accessible, easy-to-implement tests; which can be used by general practitioners, are needed.…”

Section: Accepted M Manuscriptmentioning

confidence: 99%