Retinal degeneration in experimental coronavirus retinopathy (ECOR) is associated with increased TNF-α, soluble TNFR2 and altered TNF-α signaling

Laura C. Hooper, Marian S. Chin, Barbara Detrick, John J. Hooks

Research output: Contribution to journalArticlepeer-review

Abstract

Experimental coronavirus retinopathy (ECOR) is a virally triggered model of retinal degeneration composed of both genetic and autoimmune components. Since TNF-α plays a role in immune-mediated processes we evaluated the levels of TNF-α/TNF-α receptors and the downstream signaling molecule nitric oxide (NO) during disease in both retinal degeneration susceptible BALB/c and degeneration resistant CD-1 mice. Following coronavirus injection, TNF-α mRNA was detected at higher levels within the retinas, and concentrations of TNF-α (p < 0.005) and sTNFR1 (p < 0.0005) proteins were increased within the sera of BALB/c but not CD-1 mice. While concentrations of sTNFR2 proteins were elevated in both BALB/c (p < 0.00005) and CD-1 (p < 0.005) mice compared to controls, concentrations were higher in BALB/c mice (p < 0.0005). Gene expression of iNOS while initially high in BALB/c mice decreased during the acute phase of infection, while it increased in CD-1 mice. These trends are attributable to differences in monocyte TNFR2 release (p < 0.0005) between the strains since sTNFR2 decreased (p < 0.01) levels of NO production. These studies demonstrate that retinal degeneration following viral infection is associated with increased release of TNF-α/TNF receptors combined with a down-regulation of NO. Furthermore they suggest that these molecules are involved in alterations in immune response leading to autoimmune reactivity.

Original languageEnglish (US)
Pages (from-to)65-74
Number of pages10
JournalJournal of Neuroimmunology
Volume166
Issue number1-2
DOIs
StatePublished - Sep 2005

Keywords

  • Cytokine receptors
  • Cytokines
  • Inflammation
  • Viral

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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