Purchase this article with an account.
P. L. Singh, L. Perrone, T. S. Devi; Thioredoxin Interacting Protein (TXNIP) Mediates Inflammation, Fibrosis and Gliosis in Early Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3828.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
We have recently shown that TXNIP induces histone remodeling and inflammatory gene expression in retinal endothelial cells under diabetic conditions. Here, we investigate whether TXNIP mediates inflammation, fibrosis and glial cell reactivity in early diabetic retinopathy.
Diabetes was induced in Sprague Dawley rats by Streptozotocin and maintained for 4 weeks. TXNIP was down-regulated by intravitreal injection of promoter-targeted siRNAs using cell penetrating peptides as cargo carriers, and retinal inflammation and fibrosis were determined.
Messenger RNA and protein levels of TXNIP are significantly increased in the diabetic retina when compared with normal rat retina. The increase in TXNIP is associated with enhanced levels of its downstream targets such as inflammatory cyclooxygenase 2 (Cox-2) and sclerotic fibronectin (FN). Furthermore, we observed that 4 weeks of diabetes induction in rats causes retinal muller cell gliosis (GFAP induction) and neuronal injury (synapsin 1 down-regulation and caspase-3 activation). TXNIP gene silencing blunts Cox-2, FN, and GFAP expression in the retina of diabetic rats.
The results demonstrate that TXNIP is a mediator of inflammation, fibrosis and gliosis in early diabetic retinopathy.
This PDF is available to Subscribers Only