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Qing Zhong, Renu A. Kowluru; Diabetic Retinopathy and Damage to Mitochondrial Structure and Transport Machinery. Invest. Ophthalmol. Vis. Sci. 2011;52(12):8739-8746. doi: 10.1167/iovs.11-8045.
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Mitochondrial function is controlled by membrane structure. In diabetes, retinal mitochondria are dysfunctional, and reversal of hyperglycemia fails to inhibit such changes. The goal of this study was to use anatomic and molecular biologic techniques to investigate the effect of diabetes on mitochondrial membrane structure.
Wistar rats were maintained in poor glycemic control (PC; GHb 11.2%) or good glycemic control (GC; GHb 5.5%) for 12 months or in PC for 6 months, followed by GC for an additional 6 months. The structure of the retinal mitochondria in the microvascular region was evaluated by electron microscopy (TEM) and gene expressions of mitochondrial structure–related proteins by rat mitochondrial PCR array. Representative genes were validated by real-time PCR, and their protein expression by Western blot. The results were confirmed in the retina obtained from human donors with diabetic retinopathy.
TEM showed enlarged mitochondria with partial cristolysis in the retinal microvasculature from PC rats, compared with those from normal rats. Among 84 genes, 6 retinal genes were upregulated and 12 were downregulated. PCR confirmed alternations in the gene expressions of fusion (Mfn2), carrier (Timm44 and Slc25a21), Akt1, and fission proteins (Dnm1l). Protein levels of Mfn2 and Dnm1l were consistent with their mRNA levels, but their mitochondrial abundance was decreased. Reversal of hyperglycemia failed to normalize these changes. Retinas from donors with diabetic retinopathy also presented similar patterns of changes in the gene and protein expressions.
Mitochondrial structural and transport proteins play an important role in the development of diabetic retinopathy and also in the metabolic memory phenomenon associated with its continued progression.
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