Abstract
Purpose: :
Nucleotid-related factor E2 related factor (Nrf2) is a trigger protein for the translational cellular response to oxidative stress. Nrf2 is considered a multi-organ protector. To examine the effect of Nrf2 deficiency on the retina, the eyes of 3 and 6 month old Nrf-2 knock out mice were examined histologically and by immunohistochemistry. Wild type mice and diabetic mice served as controls.
Methods: :
The eyes of 6 mice of each group were examined. Streptozotozin was used to induce experimental diabetes mellitus. Morphometric analysis of the retina was performed after enucleation on parafin embedded specimens (cell count, thickness measurement) and retinas were stained for von Willebrand factor (vWF), vascular endothelial derived growth factor (VEGF) and glial fibrillary acidic protein (GFAP). Blood vessels staining positively for each dye were counted.
Results: :
Morphometric findings included increased ganglion cell count and decreased retinal thickness in diabetic mice, but no changes in KO mice. VWF stained vascular endothelial cells of retinal vessels. The number of retinal blood vessels was lower in diabetic mice than in non diabetics and higher in KO than in WT. VEGF stained vascular endothelial cells and the blood compartment, but was not found at other sites. Healthy WT mice had more VEGF stained vessels than diabetics and KO mice. GFAP signals were found predominantly around vessels in the ganglion cell layer. They were weaker in diabetic mice than in healthy individuals, but at least equally strong in KO compared to WT.
Conclusions: :
Diabetes causes cellular oxidative stress. Diabetic changes included thinning of the retina and reduction of blood vessels. These findings may represent early diabetic retinopathy. Proliferative retinopathy does not occur in diabetic mice, and VEGF staining activity was decreased accordingly. Damage to Mueller cells is also known to occur in diabetic retinas, which may be the reason for GFAP weakening. The increase in retinal ganglion cells is unclear. Nrf2 deficiency should also cause oxidative stress. However, the findings in KO mice differed from diabetics. Retinal thickness and ganglion cell count were not changed in KO vs. WT mice. The number of blood vessels was greater, but VEGF activity was lower; thus VEGF seems not to be involved in the upregulation of vessel growth. Since GFAP signals were as in WT mice, Mueller cells function might not be altered. Nrf2 deficiency seems to improve blood supply of the retina without altering its morphology.
Keywords: oxidation/oxidative or free radical damage • retinal degenerations: cell biology • comparative anatomy