April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Thioredoxin Interacting Protein (TXNIP) Mediates Inflammation, Fibrosis and Gliosis in Early Diabetic Retinopathy
Author Affiliations & Notes
  • P. L. Singh
    Anatomy/Cell Biology and Ophthalmology,
    Wayne State Univ Sch of Med, Detroit, Michigan
  • L. Perrone
    Department of Anatomy and Cell Biology,
    Wayne State Univ Sch of Med, Detroit, Michigan
  • T. S. Devi
    Department of Anatomy and Cell Biology,
    Wayne State Univ Sch of Med, Detroit, Michigan
  • Footnotes
    Commercial Relationships  P.L. Singh, None; L. Perrone, None; T.S. Devi, None.
  • Footnotes
    Support  JDRF International
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 3828. doi:
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    • Get Citation

      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.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : 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.

Methods: : 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.

Results: : 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.

Conclusions: : The results demonstrate that TXNIP is a mediator of inflammation, fibrosis and gliosis in early diabetic retinopathy.

Keywords: diabetic retinopathy • inflammation • gene transfer/gene therapy 
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