gms | German Medical Science

102. Jahrestagung der DOG

Deutsche Ophthalmologische Gesellschaft e. V.

23. bis 26.09.2004, Berlin

Parabulbar treatment with tumor necrose factor-alpha antisense-oligonucleotides in experimental HSV-1 retinitis

Meeting Abstract

  • corresponding author A. Heiligenhaus - Ophtha-Lab and Department of Ophthalmology at St. Franziskus Hospital, Münster
  • M. Haifeng - Ophtha-Lab and Department of Ophthalmology at St. Franziskus Hospital, Münster
  • S. Wasmuth - Ophtha-Lab and Department of Ophthalmology at St. Franziskus Hospital, Münster
  • D. Bauer - Ophtha-Lab and Department of Ophthalmology at St. Franziskus Hospital, Münster

Evidenzbasierte Medizin - Anspruch und Wirklichkeit. 102. Jahrestagung der Deutschen Ophthalmologischen Gesellschaft. Berlin, 23.-26.09.2004. Düsseldorf, Köln: German Medical Science; 2004. Doc04dogFR.15.10

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dog2004/04dog300.shtml

Veröffentlicht: 22. September 2004

© 2004 Heiligenhaus et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

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.