Background: To investigate the role of tumor necrosis factor-alpha (TNF-alpha) in immunopathology and viral replication in the contralateral eye in the von Szily model of herpes simplex virus (HSV)-1 acute retinitis.
Methods: In vivo distribution was analyzed after subconjunctival injection of FITC-labeled antisense oligonucleotides (ASON). After HSV-1 (KOS) was injected in the right anterior chamber (AC) in BALB/c mice, the course of the contralateral retinitis was evaluated. The left eyes were treated with either TNF-alpha ASON, sequence-unspecific control (CON), or buffer. The ocular TNF-alpha content was quantified by ELISA. The delayed-type hypersensitivity (DTH) reaction, uptake of [3H]thymidine from regional lymph nodes (rln)- and spleen cells, serum-neutralizing antibodies, and viral titer in the eyes were evaluated.
Results: After subconjunctival injection, FITC-labeled ASON were found in the choroid and retina. In the TNF-alpha ASON-treated eyes, TNF-alpha expression and the incidence and severity of retinitis were reduced on day 8 postinfection (PI) (p < 0.05). On day 10 PI, higher viral titers were only seen in the eyes of the TNF-alpha ASON group (p < 0.05), and retinitis was slightly more severe on day 12 PI. While the HSV-1 specific [3H]thymidine uptake from rln cells was higher in the TNF-alpha ASON mice (p < 0.05), the [3H]thymidine uptake from spleen cells, the DTH response, and the neutralizing-antibody titers did not differ between the groups.
Conclusions: After regional blockade of TNF-alpha in experimental HSV-1 retinitis TNF-alpha seems to possess an antiviral capacity against HSV-1 in the contralateral eye and participates in the immunopathology of HSV-1-induced acute retinitis.
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http://dx.doi.org/10.1007/s00417-008-0839-y | DOI Listing |
Graefes Arch Clin Exp Ophthalmol
February 2012
Department of Ophthalmology, University of Cologne, Cologne, Germany.
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.
Zhonghua Yi Xue Za Zhi
March 2009
Department of Respiratory Medicine, Affiliated Hospital of Luzhou Medical College, Luzhou 646000, China.
Objective: To investigate the curative effects of inhaling signal transducer and activator of transcription 1 (STAT1) antisense oligonucleotide (ASON) on alveolitis and pulmonary fibrosis and the best administration time.
Methods: Twenty-five adult female Wistar rats were randomly divided into 5 equal groups: BLM group, undergoing intra-tracheal perfusion of BLM so as to establish animal models of alveolitis and pulmonary fibrosis and then inhaling aerosolized normal saline (NS); NS group undergoing intra-tracheal perfusion of NS and then inhaling aerosolized NS; ASON 0 d group, undergoing intra-tracheal perfusion of BLM and then inhaling aerosolized STAT1 ASON 3 ml immediately; ASON 7 d group, undergoing intra-tracheal perfusion of BLM and then inhaling STAT1 ASON 3 ml 7 days later; and ASON 14 d group undergoing intra-tracheal perfusion of BLM and then inhaling aerosolized STAT1 ASON 3 ml 14 days later. Aerosolized inhalation was repeated once every other day for 4 times.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
May 2009
Department of Respiratory Medicine, Affiliated Hospital of Luzhou Medical College, China.
Aim: To investigate the effect of aerosolized signal transducer and activator of transcription 1 (STAT1) antisense oligodeoxynucleotides (ASON) on the expression of inflammatory mediators in bronchoalveolar lavage fluid (BALF) and typeI and typeIII collagen mRNA of the bleomycin-induced rat pulmonary fibrosis.
Methods: 45 adult female Wistar rats were randomly divided into 3 groups: normal saline (NS) group, bleomycin (BLM) group and ASON group. BLM group and ASON group were intratracheally instilled with bleomycin (BLM) while NS group was instilled with NS.
Cell Mol Immunol
February 2009
The Department of Respiratory Medicine, Affiliated Hospital of Luzhou Medical College, Luzhou 646000, China.
Previous study showed that aerosolized signal transducer and activator of transcription-1 (STAT1) antisense oligodeoxynucleotide (ASON) inhibited the expression of STAT1 and ICAM-1 mRNA and protein in alveolar macrophages (AMs) and decreased the concentrations of TGF-beta, PDGF and TNF-alpha in bronchioalveolar lavage fluid (BALF) in bleomycin (BLM)-induced rat pulmonary fibrosis. Administration of STAT1 ASON ameliorated alveolitis in rat pulmonary fibrosis. However, further investigations are needed to determine whether there is an effect from administration of STAT1 ASON on fibrosis.
View Article and Find Full Text PDFPathobiology
April 2009
Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, PR China.
Objective: To investigate the effect on the pathological process of topical treatment with antisense oligonucleotides (ASON) targeting tumor necrosis factor-alpha (TNF-alpha) in experimental herpes simplex virus type-1 (HSV-1)-induced chorioretinitis of mouse eye.
Methods: 50 BALB/c mice were randomly divided into two different groups (25 mice in each group). The Von Szily model was induced in mice by inoculating 1x10(5) plaque-forming units of HSV-1 (KOS strain) into the anterior chamber of the right eye.
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