June 2020
Volume 61, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2020
Emerging functional crosstalk between the glutaredoxin system and Nrf2 antioxidant pathway: evidence from ultraviolet radiation-induced cataract formation
Author Affiliations & Notes
  • Hongli Wu
    North Texas Eye Research Institute, University of North Texas Health & Science Center, Fort Worth, Texas, United States
    University of North Texas System College of Pharmacy, Fort Worth, Texas, United States
  • Xiaobin Liu
    University of North Texas System College of Pharmacy, Fort Worth, Texas, United States
    North Texas Eye Research Institute, University of North Texas Health & Science Center, Fort Worth, Texas, United States
  • Yu Yu
    University of North Texas System College of Pharmacy, Fort Worth, Texas, United States
  • Luis Aguilera Garcia
    University of North Texas System College of Pharmacy, Fort Worth, Texas, United States
  • Myhoa Tran
    University of North Texas System College of Pharmacy, Fort Worth, Texas, United States
  • Anh Duong
    University of North Texas System College of Pharmacy, Fort Worth, Texas, United States
  • Alexander Lou
    The Village School, Houston, Texas, United States
  • Footnotes
    Commercial Relationships   Hongli Wu, None; Xiaobin Liu, None; Yu Yu, None; Luis Garcia, None; Myhoa Tran, None; Anh Duong, None; Alexander Lou, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 5133. doi:
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      Hongli Wu, Xiaobin Liu, Yu Yu, Luis Aguilera Garcia, Myhoa Tran, Anh Duong, Alexander Lou; Emerging functional crosstalk between the glutaredoxin system and Nrf2 antioxidant pathway: evidence from ultraviolet radiation-induced cataract formation. Invest. Ophthalmol. Vis. Sci. 2020;61(7):5133.

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

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Abstract

Purpose : To determine the function of glutaredoxin (Grx) system, both glutaredoxin 1 (Grx1) and glutaredoxin 2 (Grx2), in protecting the lens against ultraviolet (UV)-induced cataract formation by using Grx1/Grx2 double knockout (DKO) mice as a model.

Methods : Grx1/Grx2 DKO mice were generated by intercrossing Grx1 knockout (KO) and Grx2 KO mice. One-month old Grx1/Grx2 DKO and age-matched wild-type (WT) mice, half male and half female, were exposed to 20.6 kJ/m2 UV radiation for 15 mins to induce cataracts. Mice were euthanized at 4 days post-exposure. The degree of the cataract and lens morphology were evaluated under a dissecting microscope. Glutathione (GSH), free protein thiol (PSH), and protein glutathionylation (PSSG) levels were measured as general markers of oxidative damage. To further define the crosstalk between the Grx system and nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway, Nrf2 and its downstream target proteins were examined by using Western blot analysis.

Results : We found that UV radiation caused more severe anterior subcapsular cataract in Grx1/Grx2 DKO than that of WT mice. The opacity of the lenses in DKO mice, appeared to extend deeper into the cortical and even nuclear regions. Lenses of Grx1/Grx2 DKO mice contained significant lower levels of GSH and PSH. On the other hand, the accumulation of PSSG, a marker for protein thiol oxidation, was much higher in Grx1/Grx2 DKO group. Deletion of Grx1 and Grx2 also decreased the expression of antioxidant enzyme transcription factor regulator, Nrf2, and its downstream antioxidant genes, including catalase, superoxide dismutase (SOD), and another redox regulator of thioredoxin (Trx). These changes were especially extensive in the lens after UV exposure.

Conclusions : With combined Grx1 and Grx2 deletion, the Nrf2-dependent antioxidant response is severely impaired, causing elevation of oxidative stress that may increase the lens susceptibility to UV-induced damage.

This is a 2020 ARVO Annual Meeting abstract.

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