Renal Glomerular Podocyte Number And Foot Process Width In Aging Normal And Ove26 Transgenic Diabetic Mice

Recent studies show that numbers of renal glomerular podocytes and the width of their foot processes (FPW,) are altered in experimental and spontaneous diabetes mellitus. Podocyte nuclear density (NV) and podocytes per glomerulus (N) are generally reduced, while FPW is commonly increased, and it is hypothesized that these changes may relate to increased permeability of the blood-urine barrier. In the current study, OVE26 transgenic diabetic mice that exhibit severe proteinuria by 60 days of age, and age-matched (FVB) controls (60, 150, or 450 days) were fixed by vascular perfusion and renal cortical tissues were prepared for morphometric analyses. Point counting and Image J software analyses were used on light and transmission electron micrographs to determine glomerular volume (VG), NV, and N. FPW was determined by Image J analysis. As expected, the data showed that VG increased significantly with the duration of diabetes, but not in normal aging. At 60 and 150 days, FPW, NV, and N were not statistically distinguishable in transgenics and controls. However, at 450 days, FPW was significantly increased (82%) and NV was significantly decreased (194%) in diabetics relative to age-matched FVB mice. Moreover, at 450 days N was markedly decreased (>140%) in OVE26 mice relative to 60 day transgenics, while controls were unchanged over the same period. Interestingly, these morphological alterations do not appear temporally related to increased levels of proteinuria in this model.