June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Activation of Nrf2 suppresses inflammation and semaphorin 6A signaling in oxygen-induced retinopathy
Author Affiliations & Notes
  • Yanhong Wei
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Junsong Gong
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Elia J Duh
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Yanhong Wei, None; Junsong Gong, None; Elia Duh, None
  • Footnotes
    Support  NIH EY022683 and Research to Prevent Blindness
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2448. doi:
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    • Get Citation

      Yanhong Wei, Junsong Gong, Elia J Duh; Activation of Nrf2 suppresses inflammation and semaphorin 6A signaling in oxygen-induced retinopathy. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2448.

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

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Abstract

Purpose : Nrf2 acts as a master regulatory factor with cytoprotective antioxidant and anti-inflammatory properties. We have found that Nrf2 plays a protective role in retinal ischemia-reperfusion injury, diabetic retinopathy and oxygen-induced retinopathy (OIR). In a recent study, we demonstrated that Nrf2 promotes reparative angiogenesis via modulation of NADPH oxidase-2 (NOX2) in OIR. The objective of this study was to gain insights into the mechanism by which pharmacologic activation of Nrf2 promotes revascularization in OIR.

Methods : Mice were subjected to 75% oxygen from postnatal day 7 (P7) to 12, followed by return to room air. Mice received intravitreal injection with 1 μL 24 nM CDDO-Im at P12 and P14. The human Müller cell line MIO-M1 was pretreated with CDDO-Im for 18h, followed by stimulation with Lipopolysaccharide (LPS). Quantitative RT-PCR was used to assess mRNA expression. Human retinal endothelial cells (HREC) were transfected with siRNA for 24 hours and then seeded on collagen for tube formation assay.

Results : Pharmacologic Nrf2 activation by CDDO-Im increased revascularization and suppressed pathologic neovascularization at OIR P17. CDDO-Im treatment induced Nrf2 target gene expression while suppressing NOX2 and inflammatory cytokines. Pretreatment with CDDO-Im suppressed LPS-induced IL-1β, CCL2, and ICAM1 mRNA levels in a dose-dependent fashion in MIO-M1 cells. Retinas from mice treated with CDDO-Im exhibited decreased Sema6A mRNA levels. Plexin A2 (PlxnA2), a receptor for Sema6A, was detected in retinal blood vessels in OIR. Extracellular Sema6A treatment resulted in decreased HREC tube formation, and this effect was abrogated by siRNA-mediated knockdown of PlxnA2.

Conclusions : These studies suggest that activation of Nrf2 suppresses inflammation and Sema6A/PlxnA2 signaling, which may play a key role in mediating enhanced revascularization by CDDO-Im treatment in OIR.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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