July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Glutaredoxin 2 (Grx2) protects the retina from light-induced photoreceptor damage via regulating the endothelin receptor B (Ednrb) pathway
Author Affiliations & Notes
  • Xiaobin Liu
    Pharmaceutical Sciences, UNTHSC, Fort Worth, Texas, United States
  • Yousong Li
    Pharmaceutical Sciences, UNTHSC, Fort Worth, Texas, United States
    Department of Traditional Chinese Medicine, Shanxi Dayi Hospital, Taiyuan, Shanxi, China
  • Duenshian Wang
    Pharmaceutical Sciences, UNTHSC, Fort Worth, Texas, United States
  • Frank Ssentamu
    College of Pharmacy, University of North Texas Health Science Center, Fort Worth, Texas, United States
  • Luis Aguilera Garcia
    College of Pharmacy, University of North Texas Health Science Center, Fort Worth, Texas, United States
  • Yu Yu
    Pharmaceutical Sciences, UNTHSC, Fort Worth, Texas, United States
    Department of Obstetrics and Gynecology, The 2nd Hospital of Dalian Medical University, Dalian, Liaoning, China
  • Hongli Wu
    North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas, United States
    Pharmaceutical Sciences, UNTHSC, Fort Worth, Texas, United States
  • Footnotes
    Commercial Relationships   Xiaobin Liu, None; Yousong Li, None; Duenshian Wang, None; Frank Ssentamu, None; Luis Aguilera Garcia, None; Yu Yu, None; Hongli Wu, None
  • Footnotes
    Support  This research is supported in part by Bright Focus Foundation for Macular Degeneration (Grant No. M2015180 to Hongli Wu) and the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number R25HL125447 (to J.K.Vishwanatha).
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1700. doi:
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      Xiaobin Liu, Yousong Li, Duenshian Wang, Frank Ssentamu, Luis Aguilera Garcia, Yu Yu, Hongli Wu; Glutaredoxin 2 (Grx2) protects the retina from light-induced photoreceptor damage via regulating the endothelin receptor B (Ednrb) pathway. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1700.

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

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Abstract

Purpose : Glutaredoxin 2 (Grx2) is a glutathione-dependent oxidoreductase which is known to reduce S-glutathionylated proteins. In a previous study, we have found that Grx2 could protect the retina from light-induced retinal degeneration. To better understand the protective effects of Grx2 in the retina, our study was thus extended to analyze the full transcriptome changes of the retinal tissue in light-exposed Grx2 knockout (KO) mice.

Methods : Wild-type (WT) and Grx2 KO mice were exposed to white light at 23,000 lux for 1 hour after dark adaptation for 10 hours. The retinal damage was confirmed by the electroretinogram (ERG) recording and spectral domain optical coherence tomography (SD-OCT) measurement. Protein glutathionylation level was evaluated by Western Blot. We then compared the full transcriptome of the retinal tissue in WT and Grx2 KO mice using transcriptome shotgun sequencing (RNA-seq). The gene network was analyzed using DESeq2 pathway analysis software, and real-time PCR and Western Blot were used to confirm the selected genes of interest.

Results : Light-exposed Grx2 KO mice showed a compromised visual function as indicated by severe loss of both a- and b-wave amplitudes and the thinning of the outer nuclear layer (ONL). Protein glutathionylation level was elevated in light-exposed Grx2 KO mice. We identified thousands of genes with statistically significant expression changes in light-exposed Grx2 KO mice and classified them into cellular processes and molecular pathways. Among these pathways, many genes that are related to complement activation, inflammation, and cell survival system were significantly upregulated. These genes include Bcl-3 and Fgf2 in NF-KappaB family pathway, C4b in classical activation pathway, Jak3 and STAT3 in JAK-STAT signaling pathway, Cdkn1a in DNA damage response pathway, and endothelin 2 (Edn2) and endothelin receptor B (Ednrb) in the endothelin signaling pathway. Among these genes of interest, we found light damaged Grx2 KO mice showed significantly higher expressions of Ednrb and Edn2, in both mRNA and protein levels than their WT littermates.

Conclusions : Collectively, our results suggest that Grx2 could protect the retina from light-induced retinal degeneration. Grx2 may play an important role in protecting the retina from light-induced photoreceptor damage by regulating Ednrb-mediated pathway.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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