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John Lillvis, Manish Mishra, Kevin Rosenberg, Binit Kumar, Yang Shan, Asheesh Tewari, Renu A Kowluru; Mitochondrial DNA Damage as a Possible Biomarker of Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5190.
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© ARVO (1962-2015); The Authors (2016-present)
End organ damage from diabetes mellitus has been associated with significant derangements in oxidative metabolism. Prior work from our laboratory specifically has demonstrated that damage to mitochondrial DNA (mtDNA) is significantly increased in retinal tissue from human donors with diabetic retinopathy as compared to the non-diabetic donors. This study explores the feasibility of using mitochondrial DNA (mtDNA) damage in body fluids as a biomarker for diabetic retinopathy.
Total DNA was isolated from blood and urine obtained from streptozotocin-induced diabetic rats (8-10 months of diabetes, a duration where early histopathology characteristic of diabetic retinopathy can be seen), as well as from blood from patients with diabetic retinopathy, obtained at the time of retinal surgery. Polymerase chain reactions for long (13kb) and short (250bp) mtDNA products were performed in the total DNA. PCR products were quantified using Image J software and mtDNA damage was assessed by calculating the normalized ratio of long to short bands.
Mitochondrial DNA damage was significantly higher in the blood from diabetic rats as compared to the normal rats. Concomitant with this, mtDNA damage was also significantly higher in the urine samples of these diabetic rats. Our limited patient data showed an encouraging trend towards increased mtDNA damage in the blood of patients with diabetic retinopathy as compared with their age-matched non-diabetic counterparts.
Based upon animal model data and limited human data, mtDNA damage could be a potential biomarker of diabetic retinopathy. Future work will focus on analysis of additional blood samples, as well as collection of urine samples for analysis.
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