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Rafael S. Grajewski, Jin Li, Susanne Wasmuth, Maren Hennig, Dirk Bauer, Arnd Heiligenhaus; Intraocular Treatment With Antisense Oligonucleotides Targeting Tumor Necrosis Factor-a In Murine Herpes Simplex Virus Type 1 Retinitis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2964.
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To investigate whether inhibition of Tumor necrosis factor-alpha (TNF-a), one of the most potent pro-inflammatory cytokines, by intraocular TNF-a-antisense-oligonucleotides (ASON) affects the severity of HSV-retinitis in mice.
To determine in vivo uptake of oligonucleotides after intraocular injection, FITC-labeled TNF-a ASON was used. HSV-retinitis was induced on day 0 by injecting HSV-1 (KOS strain) into the anterior chamber (AC) of the right eyes of BALB/c mice. The left contralateral eyes received an intraocular injection of TNF-a ASON on day 7. At the same time, control groups received sequence-unspecific ASON (CON) or buffer. The clinical course of retinitis, ocular inflammatory cell-infiltration (histology), TNF-a expression in the eye (ELISA), delayed-type hypersensitivity (DTH) reaction, virus-neutralizing antibody titers in the serum, HSV-specific proliferative responses of regional lymph node cells (uptake of 3H thymidine) and viral replication in the eyes were determined.
Strong in vivo fluorescence of FITC- TNF-a ASON was detected in the choroid and retina up to 3 days after intraocular injection, but none in the regional lymph node cells. The TNF-a ASON treatment reduced the expression of TNF-a in the eye, and suppressed the incidence and severity of retinitis on day 10 after infection (p<0.05). Systemic HSV-specific immunological parameters were not significantly influenced after TNF-a ASON treatment.
The intraocular TNF-a ASON injection suppressed the ocular inflammatory cell infiltration and contralateral HSV-1 retinitis. This technical approach didn’t influence the systemic HSV-specific immune response or the antiviral protection.
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