Purchase this article with an account.
F. Lamoke, G. Ripandelli, M. Labazi, D. M. Marcus, J. J. Buccafusco, Y. Khalifa, W. Jahng, G. I. Liou, M. Bartoli; Altered Thioredoxin System in the Retina of Aged Mice Overexpressing Amyloid Beta. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3522.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
There is substantial evidence that amyloid beta (Abeta) accumulation, a known causative factor for Alzheimer’s disease (AD), may be involved in the development of age-related macular degeneration (AMD). Abeta-induced neurotoxic effects have been linked to oxygen radicals formation. The resulting oxidative stress may also be due to impairment of endogenous antioxidant enzymes such as those within the thioredoxin system (TrxS). Here we assessed the expression level and the activity of thioredoxin 1 (Trx-1), thioredoxin inhibitory protein (TXNIP) and thioredoxin reductase (TrxR1) in relation to retinal stress parameters in transgenic mice overexpressing Abeta.
Retinas from transgenic mice (TG) overexpressing presenilin (PS1) and amyloid precursor protein (APP) (APP695 -PSEN1, Jackson Lab.) were compared to age-matched wild type mice (WT) (13±2 months old). Retinal production of Abeta (1-40) and glial fibrillary acidic protein (GFAP) was assessed by immunohistochemistry. TUNEL assay was used to determine retinal cell death. Expression levels of Abeta, Trx-1, TXNIP, TrxR1 and phosphorylated ASK-1 were determined by Western analysis. TrxR1 activity and lipid peroxidation were assayed by using commercially available assay kits (Cayman).
Abeta production was enhanced in the retinal pigmented epithelium of TG mice as compared to WT. TUNEL assay did not show significant differences in retinal cell death in TG mice, however a significant increase in GFAP formation was detected particularly in Muller cells. Lipid peroxidation was elevated in TG mice as compared to WT (p<0.05) and this correlated with enhanced expression levels of Trx-1 and TXNIP. Activity of TrxR1 was significantly reduced (50%, p<0.03) in TG versus WT mice. Trx-1 activity was reduced as observed by increased phosphorylation of ASK1.
Our data suggests that Abeta effects on retinal oxidative stress and subsequent induction of gliosis, as suggested by elevated GFAP expression, may involve impairment of TrxS and possibly implicate this mechanism in the pathogenesis of AMD.
This PDF is available to Subscribers Only