Extracellular superoxide dismutase (SOD3) regulates oxidative stress at the vitreoretinal interface

Katherine J. Wert, Gabriel Velez, Madeline R. Cross, Brett A. Wagner, Melissa L. Teoh-Fitzgerald, Garry R. Buettner, J. Jason McAnany, Alicia Olivier, Stephen H. Tsang, Matthew M. Harper, Frederick E. Domann, Alexander G. Bassuk, Vinit B. Mahajan

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Oxidative stress is a pathogenic feature in vitreoretinal disease. However, the ability of the inner retina to manage metabolic waste and oxidative stress is unknown. Proteomic analysis of antioxidants in the human vitreous, the extracellular matrix opposing the inner retina, identified superoxide dismutase-3 (SOD3) that localized to a unique matrix structure in the vitreous base and cortex. To determine the role of SOD3, Sod3-/- mice underwent histological and clinical phenotyping. Although the eyes were structurally normal, at the vitreoretinal interface Sod3-/- mice demonstrated higher levels of 3-nitrotyrosine, a key marker of oxidative stress. Pattern electroretinography also showed physiological signaling abnormalities within the inner retina. Vitreous biopsies and epiretinal membranes collected from patients with diabetic vitreoretinopathy (DVR) and a mouse model of DVR showed significantly higher levels of nitrates and/or 3-nitrotyrosine oxidative stress biomarkers suggestive of SOD3 dysfunction. This study analyzes the molecular pathways that regulate oxidative stress in human vitreous substructures. The absence or dysregulation of the SOD3 antioxidant at the vitreous base and cortex results in increased oxidative stress and tissue damage to the inner retina, which may underlie DVR pathogenesis and other vitreoretinal diseases.

Original languageEnglish (US)
Pages (from-to)408-419
Number of pages12
JournalFree Radical Biology and Medicine
Volume124
DOIs
StatePublished - Aug 20 2018

Keywords

  • Antioxidant
  • Diabetic retinopathy
  • Extracellular matrix
  • Knockout mouse
  • Metabolic dysregulation
  • Proteomics
  • Vitreous base
  • Vitreous cortex
  • Vitreous substructures

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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  • Cite this

    Wert, K. J., Velez, G., Cross, M. R., Wagner, B. A., Teoh-Fitzgerald, M. L., Buettner, G. R., McAnany, J. J., Olivier, A., Tsang, S. H., Harper, M. M., Domann, F. E., Bassuk, A. G., & Mahajan, V. B. (2018). Extracellular superoxide dismutase (SOD3) regulates oxidative stress at the vitreoretinal interface. Free Radical Biology and Medicine, 124, 408-419. https://doi.org/10.1016/j.freeradbiomed.2018.06.024