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5 Oxidative stress and epigenetic modifications in DR Long-term hyperglycemia triggers epigenetic modifications, which, without altering the DNA sequence, regulate gene expression through mechanisms like DNA methylation, histone modification, and noncoding RNA expression (105)

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2 Types of hypoxia and crosstalk with mitochondria 2.1 Physiological hypoxia The oxygen level can vary greatly within cells of different organs or tissues, ranging from 1% to 13% in what is known as a physical gradient (Kumar and Choi, 2015