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Qing Zhong, Renu Kowluru; Diabetic Retinopathy And Mitochondrial Structure Proteins. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4452.
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Our previous studies have shown that in the pathogenesis of diabetic retinopathy, retinal mitochondria are dysfunctional, their DNA (mtDNA) is damaged, and the import of DNA repair enzymes to the mitochondria is decreased. Mitochondria are composed of outer membrane and inner membrane, and the structure of the membranes controls mitochondrial integrity, transport, fusion-fission and aerobic respiration. This study is to investigate the effect of diabetes on retinal mitochondrial membrane structure proteins.
Gene expressions of mitochondrial structure-related proteins were measured in the retina obtained from diabetic rats (streptozotocin-induced, 12 months duration) and age-matched normal rats using rat mitochondrial PCR array (PARN-087 SABiosciences). Representative genes were validated by Taqman realtime quantitative PCR (qPCR). The results were confirmed in the retina obtained from donors with diabetic retinopathy by quantifying gene and protein expressions of the representative proteins.
Among 84 mitochondrial structure-related genes, diabetes down-regulated 13 genes in the retina, and qPCR results confirmed the decreased expressions of solute carrier slc25a21, peptide carrier tim44, antiapoptotic factor akt, and mitochondrial fusion protein mitofusin 2 (mfn2). In contrast, some of the genes from mitochondrial fission family and solute and peptide carrier families were upregulated, and qPCR results confirmed such changes. Consistent with this, retina from donors with diabetic retinopathy also presented similar down-regulation of slc25a21, tim44, mfn2 and akt, and upregulation of solute carrier slc25a12 and mitochondrial fission protein dynamin 1-like protein (Dnm1L) as compared to the values obtained from age-matched non diabetic donors. On a subcellular level, diabetic donors with retinopathy, relative to non-diabetic donors, had subnormal protein expressions of tim44, tom34 and mfn2 in their retinal mitochondria.
Retinal mitochondrial dysfunction in diabetes could be due to alterations in fusion-fission and carrier proteins. Strategy targeting to improve mitochondrial fusion-fission and import machinery may help to halt the development of diabetic retinopathy.
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