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DOI: 10.1055/s-0035-1549510
Hyperglycemic memory – Mechanisms relevant to the diabetic retina
Clinical and experimental evidence suggests that hyperglycemic memory is part of the complex pathogenesis of diabetic retinopathy. Perpetuation of oxidative stress, irreversible accumulation of AGEs and hyperglycemia-induced epigenetic changes are possible underlying mechanisms. In the present study we address the gap between cellular memory experiments, reflecting days, and animal and human disease, representing years.
STZ (140 mg/kg/body weight) induced diabetic C57Bl6 mice (n = 4 – 6/group) with a hyperglycemia (30 mmol/l) duration of 12 weeks were utilized (DC12W; NC12W = Control). Group B12W was treated in parallel with Benfotiamin. After 6 weeks of hypergycemia group Tx was treated with beta-cell transplantation for euglycemic-reentry and group B6W with Benfotiamin for the following 6 weeks. Pericyte coverage of the retinal vascular network and retinal whole genome expression (Affymetrix GeneChip Mouse Gene 2.0 ST), using Ingenuity Pathway software, were analyzed.
Transplanted mice showed a reduction of HbA1c from ˜11,8% in the diabetic group to ˜6,3% (Control: ˜5,5%). Pericyte numbers were lowered in all groups compared to the control (Pericyte/mm2; NC12W: 1981; DC12W: 1571; Tx: 1606; B12W: 1681; B6W: 1559; p < 0,0001). Top 3 affected signaling networks were:
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RNA Post-Transcriptional Modification, Cancer, Cellular Movement
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Cancer, Organismal Injury and Abnormalities, Cardiac Dysplasia
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Developmental Disorder, Hereditary Disorder, Inflammatory Disease
In conclusion, we established a mouse model of retinal Hyperglycemic Memory. No improvement of early vascular damage markers after euglycemic-reentry or Benfotiamin treatment was detected. In addition, we found genes irreversibly altered after euglycemic-reentry.