Retinal degeneration in experimental coronavirus retinopathy (ECOR) is associated with increased TNF-alpha, soluble TNFR2 and altered TNF-alpha signaling.
Experimental coronavirus retinopathy (ECOR) is a virally triggered model of retinal degeneration composed of both genetic and autoimmune components. Since TNF-alpha plays a role in immune-mediated processes we evaluated the levels of TNF-alpha/TNF-alpha 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-alpha mRNA was detected at higher levels within the retinas, and concentrations of TNF-alpha (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-alpha/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.
Hooper
Laura C
LC
Laboratory of Immunology, Immunology and Virology Section, National Eye Institute, National Institutes of Health, NIH Bldg 10, Rm 6N228, 10 Center Drive, Bethesda, MD 20892, USA.
Chin
Marian S
MS
Detrick
Barbara
B
Hooks
John J
JJ
D000818:Animals; D018352:Coronavirus Infections / Q000150:complications* / Q000378:metabolism; D015870:Gene Expression; D007150:Immunohistochemistry / Q000379:methods; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D009000:Monocytes / Q000378:metabolism; D006517:Murine hepatitis virus; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D009994:Osmolar Concentration; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000737:chemistry / Q000378:metabolism*; D012160:Retina / Q000378:metabolism; D012162:Retinal Degeneration / Q000821:virology*; D015398:Signal Transduction; D012995:Solubility; D013194:Staining and Labeling; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
D016898:Interferon-alpha; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse