Epigenetic Modification ofSod2in the Development of Diabetic Retinopathy and in the Metabolic Memory: Role of Histone Methylation

Retinopathy is a debilitating vascular complication of diabetes. As with other diabetic complications, diabetic retinopathy (DR) is characterized by the metabolic memory, which has been observed both in DR patients and in DR animal models. Evidences have provided that after a period of poor glucose control insulin or diabetes drug treatment fails to prevent the development and progression of DR even when good glycemic control is reinstituted (glucose normalization), suggesting a metabolic memory phenomenon. Recent studies also underline the role of epigenetic chromatin modifications as mediators of the metabolic memory. Indeed, epigenetic changes may lead to stable modification of gene expression, participating in DR pathogenesis. Moreover, increasing evidences suggest that environmental factors such as chronic hyperglycemia are implicated DR progression and may also affect the epigenetic state. Here we review recent findings demonstrating the key role of epigenetics in the progression of DR. Further elucidation of epigenetic mechanisms, acting both at the cis- and trans-chromatin structural elements, will yield new insights into the pathogenesis of DR and will open the way for the discovery of novel therapeutic targets to prevent DR progression.

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Role of histone acetylation in the development of diabetic retinopathy and the metabolic memory phenomenon

Journal of Cellular Biochemistry ◽

10.1002/jcb.22644 ◽

2010 ◽

Vol 110 (6) ◽

pp. 1306-1313 ◽

Cited By ~ 85

Author(s):

Qing Zhong ◽

Renu A. Kowluru

Keyword(s):

Diabetic Retinopathy ◽

Histone Acetylation ◽

Metabolic Memory

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Epigenetic Modifications and Diabetic Retinopathy

BioMed Research International ◽

10.1155/2013/635284 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 53

Author(s):

Renu A. Kowluru ◽

Julia M. Santos ◽

Manish Mishra

Keyword(s):

Diabetic Retinopathy ◽

Dna Methyltransferase ◽

Epigenetic Modification ◽

Epigenetic Modifications ◽

Mitochondrial Superoxide ◽

Micro Rnas ◽

Genes Encoding ◽

Lysine Demethylase ◽

Metalloproteinase 9

Diabetic retinopathy remains one of the most debilitating chronic complications, but despite extensive research in the field, the exact mechanism(s) responsible for how retina is damaged in diabetes remains ambiguous. Many metabolic pathways have been implicated in its development, and genes associated with these pathways are altered. Diabetic environment also facilitates epigenetics modifications, which can alter the gene expression without permanent changes in DNA sequence. The role of epigenetics in diabetic retinopathy is now an emerging area, and recent work has shown that genes encoding mitochondrial superoxide dismutase (Sod2) and matrix metalloproteinase-9 (MMP-9) are epigenetically modified, activates of epigenetic modification enzymes, histone lysine demethylase 1 (LSD1), and DNA methyltransferase are increased, and the micro RNAs responsible for regulating nuclear transcriptional factor and VEGF are upregulated. With the growing evidence of epigenetic modifications in diabetic retinopathy, better understanding of these modifications has potential to identify novel targets to inhibit this devastating disease. Fortunately, the inhibitors and mimics targeted towards histone modification, DNA methylation, and miRNAs are now being tried for cancer and other chronic diseases, and better understanding of the role of epigenetics in diabetic retinopathy will open the door for their possible use in combating this blinding disease.

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