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Faulty homocysteine recycling in diabetic retinopathy

Eye and Vision 2020年第1期7卷 36-46页

作者： renu a.kowluru Ghulam Mohammad Nikhil Sahajpal Department of Ophthalmology Visual Sciences and Anatomical SciencesWayne State University4717 St.AntoineDetroitMI 48201USA

Background:Although hyperglycemia is the main instigator in the development of diabetic retinopathy,elevated circulating levels of a non-protein amino acid,homocysteine,are also associated with an increased risk of *** is recycled back to methionine by methylenetetrahydrofolate reductase(MTHFR)and/or transsulfurated by cystathionineβ-synthase(CBS)to form *** and other transsulfuration enzyme cystathionine-γ-lyase(CSE),through desulfuration,generates H_(2)*** cycle also regulates DNA methylation,an epigenetic modification associated with the gene *** aim of this study was to investigate homocysteine and its metabolism in diabetic ***:Homocysteine and H_(2)S levels were analyzed in the retina,and CBS,CSE and MTHFR in the retinal microvasculature from human donors with established diabetic *** damage was evaluated in retinal microvessels by quantifying enzymes responsible for maintaining mitochondrial dynamics(fission-fusionmitophagy).DNA methylation status of CBS and MTHFR promoters was examined using methylated DNA immunoprecipitation *** direct effect of homocysteine on mitochondrial damage was confirmed in human retinal endothelial cells(HRECs)incubated with 100μM ***:Compared to age-matched nondiabetic control human donors,retina from donors with established diabetic retinopathy had~3-fold higher homocysteine levels and~50%lower H_(2)S *** enzymes important for both transsulfuration and remethylation of homocysteine including CBS,CSE and MTHFR,were 40–60%lower in the retinal microvasculature from diabetic retinopathy *** the mitochondrial fission protein,dynamin related protein 1,and mitophagy markers optineurin and microtubule-associated protein 1A/1B-light chain 3(LC3),were upregulated,the fusion protein mitofusin 2 was *** the same retinal microvessel preparations from donors with diabetic retinopathy,DNA at the prom

关键词： Diabetic retinopathy DNA methylation Homocysteine Hydrogen sulfide Mitophagy Epigenetics Mitochondria Oxidative stress Retina

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Correction to: Faulty homocysteine recycling in diabetic retinopathy

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Eye and Vision 2020年第1期7卷 109-110页

作者： renu a.kowluru Ghulam Mohammad Nikhil Sahajpal Department of Ophthalmology Visual Sciences and Anatomical SciencesWayne State University4717 St.AntoineDetroitMI 48201USA

Correction to:Eye and Vision(2020)7:4 https://***/10.1186/s40662-019-0167-9 In the original publication of this article[1]Fig.2b is *** correct Fig.2 is as *** original publication has been corrected.

关键词： correct corrected diabetic

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Contribution of epigenetics in diabetic retinopathy

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Science China(Life Sciences) 2015年第6期58卷 556-563页

作者： kowluru renu A. MISHRA Manish Kresge Eye Institute Wayne State University

Diabetes has become the epidemic of the 21 st century, and with over 90% patients with diabetes becoming at a risk of developing retinopathy, diabetic retinopathy has emerged as a major public health concern. In spite of cutting edge research in the field, how retina and its vasculature are damaged by the diabetic milieu remains ambiguous. The environmental factors, life style or disease process can also bring in modifications in the DNA, and these epigenetic modifications either silence or activate a gene without altering the DNA sequence. Diabetic environment up- or downregulates a number of genes in the retina, and emerging research has shown that it also facilitates epigenetic modifications. In the pathogenesis of diabetic retinopathy, the genes associated with important enzymes(e.g., mitochondrial superoxide dismutase, matrix metalloproteinase-9 and thioredoxin interacting protein) and transcriptional factors are epigenetically modified, the enzymes responsible for these epigenetic modifications are either activated or inhibited, and the levels of micro RNAs are altered. With epigenetic modifications taking an important place in diabetic retinopathy, it is now becoming critical to evaluate these modifications, and understand their impact on this slow progressing blinding disease.

关键词： diabetic retinopathy epigenetic modifications histone acetylation histone methylation miRNA

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