Antisense-oligonucleotides targeting tumor necrosis factor-alpha in murine herpes simplex virus type 1 retinitis

Dr. Li, Jin

Dateibereich 15817

3,44 MB in einer Datei, zuletzt geändert am 12.11.2012

Dateiliste / Details

DateiDateien geändert amGröße
jin_li_diss.pdf13.12.2006 11:41:173,44 MB

Dateibereich 15818

4,55 MB in 2 Dateien, zuletzt geändert am 13.12.2006

Dateiliste / Details

DateiDateien geändert amGröße
Abstracts.doc07.12.2006 08:34:2927 KB
thesisnew.doc13.12.2006 11:43:444,52 MB
Purpose: To investigated whether topical tumor necrosis factor-alpha (TNF-α)-antisense-oligonucleotides (ASON) treatment might affect the course of contralateral HSV-retinitis. Methods: In vivo uptake was determined after subconjunctival (s.c.) injection of FITC-labeled TNF-α-ASON. BALB/c mice were injected in the AC of the right eyes with HSV-1 (KOS); the left eyes were injected s.c. 3 times with TNF-α-ASON; sequence-unspecific control (C) ON or buffer. The clinical course of HSV-R, ocular inflammatory cell-infiltration, uptake of [3H]thymidine from rLN cells and viral replication in the eyes were analyzed. Results: In vivo, FITC-TNF-α-ASON was found in the choroid and retina up to 7 days after s.c. injection, but also in the rLN. After s.c. TNF-α-ASON injection, expression of TNF-α was reduced in the ipsilateral eyes and rNL. TNF-α-ASON injection reduced the incidence and severity of early chorioretinitis and of the inflammatory cell infiltration and CD-11b cells in the choroid and retina of the treated eye. On day 10 PI, the virus titers, inflammatory cell infiltration and HSV-R had increased in the TNF-α-ASON treated eyes, while the HSV-1 specific [3H]thymidine uptake from rLN cells was decreased and DTH response did not differ between the PBS, CON and TNF-α-ASON groups. Conclusions: Topical TNF-α-ASON-injection reduced early ocular inflammatory cell infiltration, but delayed the virus clearance and increased the severity of HSV-retinitis in the treated eyes. The antisense technique is a useful experimental approach for the topical application of TNF-α in experimental HSV-1 retinitis.
Lesezeichen:
Permalink | Teilen/Speichern
Dokumententyp:
Wissenschaftliche Abschlussarbeiten » Dissertation
Fakultät / Institut:
Medizinische Fakultät
Dewey Dezimal-Klassifikation:
600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit
Stichwörter:
TNF-alpha, herpes simplex virus, retinitis, murine, ASON
Beitragende:
Univ.-Prof. Dr. med. Heiligenhaus, Arnd [Betreuer(in), Doktorvater]
Univ.-Prof. Dr. rer. nat. Dittmer, Ulf [Gutachter(in), Rezensent(in)]
Sprache:
Englisch
Kollektion / Status:
Dissertationen / Dokument veröffentlicht
Datum der Promotion:
15.08.2006
Dokument erstellt am:
29.09.2006
Dateien geändert am:
12.11.2012
Medientyp:
Text