Reduced Histopathological Alterations in Long-Term Diabetic TNF-R Deficient Mice

Abstract

Abstract: : Purpose: Inflammation seems to play a major role in the pathogenesis of diabetic retinopathy. Previous studies have demonstrated that inhibition of TNF alpha can reduce leukocyte adhesion and vascular leakage (Joussen et al. 2002), but also apoptotic endothelial cell death in diabetes. Here we investigate the effect of long-term inhibition of TNF alpha on the development of diabetic vascular lesions. Methods: Using a mouse model of long-term galactose induced hyperhexosemia in mice, we examined the role of TNF-R p55 and TNF-R p75 in the development of retinal vascular lesions by trypsin digest preparations. Results: Galactosemia of up to 18 month causes pericyte and endothelial cell loss and formation of acellular capillaries. In contrast, both TNF-R deficient mice strains demonstrated only few alterations of the retinal vessels. Both pericyte- and endothelial cell numbers were significantly higher compared to galactose fed wild-type animals. After 18 month of galactosemia the total capillary length, which was reduced in wildtype mice, was not significantly altered in both TNF-R deficient mice strains. Conclusions: The current study demonstrates that inhibition of TNF alpha via both TNF-Rp55 and TNF-Rp75 can prevent histopathological alterations in long term diabetic mice. These data underscore the potential utility of anti-inflammatory treatment in diabetic retinopathy.

Keywords: diabetic retinopathy • inflammation