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Publication : Retinal capillary basement membrane thickness in diabetic mice genetically modified at the haptoglobin locus.

First Author  Miller-Lotan R Year  2007
Journal  Diabetes Metab Res Rev Volume  23
Issue  2 Pages  152-6
PubMed ID  16742000 Mgi Jnum  J:127997
Mgi Id  MGI:3765311 Doi  10.1002/dmrr.654
Citation  Miller-Lotan R, et al. (2007) Retinal capillary basement membrane thickness in diabetic mice genetically modified at the haptoglobin locus. Diabetes Metab Res Rev 23(2):152-6
abstractText  BACKGROUND: Individuals with diabetes mellitus (DM) homozygous for the haptoglobin (Hp) 1 allele are at decreased risk of retinopathy as compared to DM individuals with the Hp 2 allele. We sought to recapitulate these findings in DM mice genetically modified at the Hp locus. METHODS: An early morphological characteristic of the microangiopathy seen in diabetic retinal disease is retinal capillary basement membrane (RCBM) thickening. RCBM thickness as assessed by electron microscopy was performed on a total of 12 eyes taken from three mice in each of the four study groups (three eyes from C57Bl/6 Hp 1 and C57Bl/6 Hp 2 mice with and without streptozotocin-induced diabetes). RESULTS: The non-parametric Kruskal-Wallis ANOVA test demonstrated that there was a highly significant difference between the four groups of mice (P < 0.0001). Mann-Whitney tests for specific pair-wise comparisons demonstrated that there was no significant difference in the RCBM thickness between Hp 1 and Hp 2 mice (p = 0.70) or between DM Hp 1 and non-DM Hp 1 mice (p = 0.42). However, induction of diabetes resulted in a marked increase in RCBM thickness in Hp 2 mice compared to non-DM Hp 2 mice (p = 0.0004) and compared to DM Hp 1 mice (p = 0.0005). CONCLUSIONS: A highly significant increase in RCBM thickness was observed in DM mice with the Hp 2 genotype. These data provide important support for association studies done in humans showing an increased prevalence of diabetic retinopathy in individuals with the Hp 2 genotype.
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