September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Possible Roles of Glutaredoxin 2 (Grx2) in the Pathogenesis of Diabetic Retinopathy
Author Affiliations & Notes
  • Christy Xavier
    North Texas Eye Research Institute, Fort Worth, Texas, United States
    Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, Texas, United States
  • Xiaobin Liu
    North Texas Eye Research Institute, Fort Worth, Texas, United States
    Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, Texas, United States
  • Liangjun Yan
    Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, Texas, United States
  • Jinzi Wu
    Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, Texas, United States
  • Hongli Wu
    North Texas Eye Research Institute, Fort Worth, Texas, United States
    Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, Texas, United States
  • Footnotes
    Commercial Relationships   Christy Xavier, None; Xiaobin Liu, None; Liangjun Yan, None; Jinzi Wu, None; Hongli Wu, Reata Pharmaceuticals (F)
  • Footnotes
    Support  BrightFocus Foundation for Macular Degeneration (Grant No. M2015180 to Hongli Wu)
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 5450. doi:
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    • Get Citation

      Christy Xavier, Xiaobin Liu, Liangjun Yan, Jinzi Wu, Hongli Wu; Possible Roles of Glutaredoxin 2 (Grx2) in the Pathogenesis of Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5450.

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

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Abstract

Purpose : Diabetic retinopathy (DR) is the leading cause of blindness in developed countries, affecting nearly 700,000 people worldwide. Glutaredoxin 2 (Grx2) is a mitochondrial thioltransferase that protects protein thiols from oxidative damage. Dysfunction or deficiency of Grx2 has been linked to increased cell death and a variety of retinopathies, including age-related retinal degeneration. This study seeks to explore the relationship between Grx2 and diabetic retinopathy.

Methods : Wistar rats were treated with STZ for 4 weeks, and neural retinas were collected and tested for Grx2, thioredoxin (Trx), and thioredoxin binding protein-2 (TBP-2) expression and activity. Retinal angiography and glycation immunoblotting were used to verify diabetic retinopathy condition. Mitochondrial, cytoplasmic, and nuclear isolation was performed to see the translocation and expression of Nrf2 and DJ-1 and protein glutathionylation (PSSG) formation.

Results : Glycation was significantly increased in diabetic samples than control samples, indicating an advanced diabetic state. Although Nrf2 was increased in the cytoplasm, Nrf2 translocation was significantly hindered, leading to decreased Grx2 and Trx levels and increased TBP-2 expression. DJ-1, a novel glyoxylase that also mediates Nrf2 activation, was also subsequently decreased.

Conclusions : Decreased DJ-1 and Nrf2 expression and translocation may lead to Grx2 deficiency in the diabetic retina. Loss of Grx2 may lead to disturbed thiol redox homeostasis in the retina and eventually cause diabetic retinopathy.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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