The Role of Mitochondrial DNA (mtDNA) in the Development of Diabetic Retinopathy (DR): A Systematic Review

Abstract Diabetic Retinopathy (DR) is the most prevalent health problem, which is influenced by environmental and genetic factors with an increasing prevalence. The current systematic review is focused on mtDNA modification, including polymorphism and mutation/deletion, with a direct effect on DR. This systematic search was initially done through PubMed, Cochrane, EMBASE, SCOPUS, and Web of Science without a restriction on the years of publication. The terms searched included ‘‘mtDNA’’, ‘‘mitochondrial DNA’’, ‘‘diabetes’’, ‘‘diabetic’’, ‘‘retina’’, and ‘‘diabetic retinopathy’’. Animal, cohort, cross-sectional, and in vitro studies, as well as case series, case reports, review articles, and Letters to Editor were excluded from this research. From ۱۵۲۸ resulting searched articles, only ۱۲ papers were finally chosen as the case-control studies considering  mtDNA gene and DR. Actually, of these ۱۲ articles, ۸ studies were concerned with mtDNA polymorphisms (UCP۱, UCP۲, ROMO-۱, and Mn-SOD) and ۴ articles were related to mtDNA mutation (A۳۲۴۳G mutation in tRNALeu(UUR) gene and mtDNA deletion (ΔmtDNA ۴۹۷۷)). Some conflicting results were found between the selected genetic modifications of mtDNA, such as Mn-SOD, UCP۱, ΔmtDNA ۴۹۷۷, tRNALeu (UUR), and ROMO-۱. Finally, A۳۲۴۳G mutation in the tRNALeu (UUR) gene and rs۶۶۰۳۳۹ and V۱۶A polymorphisms of UCP۲ and Mn-SOD genes were respectively considered as the most important factors in the pathogenesis of DR.Â