Article
Parabulbar treatment with tumor necrose factor-alpha antisense-oligonucleotides in experimental HSV-1 retinitis
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Published: | September 22, 2004 |
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Outline
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Objective
Injection of herpes simplex virus in the anterior chamber (von Szily model) results in an ipsilateral iritis and a contralateral herpes simplex retinitis (HSR). In this study, the effect of a local treatment of the contralateral eye with tumor necrosis factor-alpha (TNF-α)-antisense-oligonucleotides (ASON) on the HSR was investigated.
Methods
Splenic cells were incubated in vitro with TNF-α-ASON, sequence-unspecific control-oligonucleotides (CON) or medium; the uptake of FITC-oligonucleotides was analyzed by FACS; the TNF-α-content in the supernatant was studied by ELISA. FITC-TNF-α-ASON or unbound FITC was injected in the parabulbar space (p.b.). Paraffin-sections of the treated eyes were studied by fluorescent microscopy. HSV-1 (KOS) was injected in the anterior chamber of the right eye in BALB/c mice. On the days -1, 1 und 4, the contralateral eye was injected p.b. with TNF-α-ASON; control mice received p.b. CON or buffer, or were only infected. HSR-development was judged clinically, and the inflammatory cell-infiltration was studied by histology.
Results
FITC-oligonucleotides were taken-up by spleen cells. In contrast to medium and CON, TNF-α-ASON markedly reduced the TNF-α-production in vitro, without being zytotoxic. While the choroid and retina were fluo-positive 7 days after p.b. injection of FITC-TNF-α-ASON, they were fluo-negative already 2 days after injection of unbound FITC. The treatment with TNF-α-ASON reduced the development of HSR as compared to CON or PBS, and the numbers of inflammatory cells in the choroid and retina were decreased.
Conclusions
TNF-α-ASON were taken-up by spleen cells and reduced the TNF-α-secretion in vitro. After p.b. TNF-α-ASON-injection, ASON was detected in the choroid and retina and the course of the herpes simplex retinitis was improved.