TEM stereometric analyses of glomeruli in aging OVE26 transgenic diabetic mice.

ABSTRACT

BACKGROUND/AIMS: Glomerular lesions in diabetic nephropathy (DN) have been studied in numerous murine diabetic models, but the critical feature of aging is often absent. Since histopathology indicates that in mice, DN glomerular lesions may just begin to develop at about 5 months of age, we utilized the long-lived OVE26 transgenic diabetic model for stereometric analyses of DN glomerulopathic aging. METHODS: Albuminuria was determined by ELISA, and transmission electron microscopy stereometry was utilized exclusively to demonstrate changes in glomerular cell density and number, and alterations in the glomerular filtration barrier in OVE26 mice at 60, 150, and 450 days of age. RESULTS: Compared to age-matched controls, albuminuria in diabetic mice is significant at 60 days. At 150 days, glomerular volume and mesangial, endothelial and total cell numbers, and podocyte effacement are significantly increased, while podocyte, endothelial, and total cell density are significantly decreased. Endothelial fenestrations are decreased, and glomerular basement membrane thickness is increased. At 450 days, stereometric alterations are exacerbated. CONCLUSION: Our data indicate that in OVE26 mice, albuminuria precedes morphological glomerular lesions and could be due to early-onset hyperglycemia. Moreover, in this model, most DN glomerulopathic lesions occur relatively late in life, and it is possible that they may result from prolonged hyperglycemia-induced oxidative stress.