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Intravitreal treatment with antisense oligonucleotides targeting tumor necrosis factor-α in murine herpes simplex virus type 1 retinitis.
Grajewski, Rafael S; Li, Jin; Wasmuth, Susanne; Hennig, Maren; Bauer, Dirk; Heiligenhaus, Arnd.
Afiliación
  • Grajewski RS; Department of Ophthalmology, University of Cologne, Cologne, Germany.
Graefes Arch Clin Exp Ophthalmol ; 250(2): 231-8, 2012 Feb.
Article en En | MEDLINE | ID: mdl-22072377
BACKGROUND: Tumor necrosis factor alpha (TNF-α) is a proinflammatory cytokine known to participate in intraocular inflammatory disease. This study investigated whether treatment with intravitreal antisense-oligonucleotides (ASON) targeting TNF-α mRNA affects the progression of herpes simplex virus 1 (HSV-1) retinitis in mice. METHODS: The in vivo uptake of the oligonucleotid after intravitreal injection was determined with FITC-labeled TNF-α ASON. HSV-retinitis was induced on day 0 by the injection of HSV-1 (KOS strain) into the anterior chamber (AC) of the right eyes of BALB/c mice (von Szily model). The left contralateral eyes were injected intravitreally on day 7 with TNF-α ASON, sequence-unspecific control ASON (CON), or buffer. The clinical course of retinitis, ocular inflammatory cell-infiltration, TNF-α expression in the eye by ELISA, delayed-type hypersensitivity (DTH) reaction, virus-neutralizing antibody titers in the serum, uptake of [3H]thymidine from regional lymph node (rln) cells, and viral content in the eyes were determined. RESULTS: In vivo, strong fluorescence of FITC- TNF-α ASON was detected in the choroid and retina up to 3 days after intravitreal injection, but none in the rln. After treatment of eyes with ASON, decreased expression of TNF-α in the eye, and reduced incidence and severity of retinitis on day 10 after infection (P < 0.05) could be found. The other parameters were not significantly influenced after TNF-α ASON treatment. CONCLUSIONS: TNF-α participates in the pathology of HSV-1 retinitis. Local inhibition of TNF-α mRNA by intraocular TNF-α ASON injection did not influence the systemic HSV-specific immune response or the antiviral response in the eye, but reduced ocular inflammatory bystander damage.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Infecciones Virales del Ojo / Síndrome de Necrosis Retiniana Aguda / Oligonucleótidos Antisentido / Factor de Necrosis Tumoral alfa / Herpesvirus Humano 1 / Herpes Simple Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Graefes Arch Clin Exp Ophthalmol Año: 2012 Tipo del documento: Article País de afiliación: Alemania

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Infecciones Virales del Ojo / Síndrome de Necrosis Retiniana Aguda / Oligonucleótidos Antisentido / Factor de Necrosis Tumoral alfa / Herpesvirus Humano 1 / Herpes Simple Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Graefes Arch Clin Exp Ophthalmol Año: 2012 Tipo del documento: Article País de afiliación: Alemania