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

Rachel Miller-Lotan, Benjamin Miller, Farid Nakhoul, Doron Aronson, Roy Asaf, Andrew P. Levy

Research output: Contribution to journalArticlepeer-review


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 C57B1/6 Hp 1 and C57B1/6 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.

Original languageEnglish
Pages (from-to)152-156
Number of pages5
JournalDiabetes/Metabolism Research and Reviews
Issue number2
StatePublished - Feb 2007
Externally publishedYes


  • Diabetic vascular complications
  • Genetic susceptibility
  • Haptoglobin
  • Hemoglobin

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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