Retinal capillary basement membrane thickness in diabetic mice genetically modified at the haptoglobin locus.
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.
Miller-Lotan
Rachel
R
Technion-Israel Institute of Technology, Haifa, Israel.
Miller
Benjamin
B
Nakhoul
Farid
F
Aronson
Doron
D
Asaf
Roy
R
Levy
Andrew P
AP
D000818:Animals; D001485:Basement Membrane / Q000473:pathology* / Q000648:ultrastructure; D002196:Capillaries / Q000473:pathology* / Q000648:ultrastructure; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D003925:Diabetic Angiopathies / Q000473:pathology; D006242:Haptoglobins / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012171:Retinal Vessels / Q000473:pathology* / Q000648:ultrastructure
D006242:Haptoglobins