Phosphorothioate oligonucleotides induction into experimental choroidal neovascularization by HVJ-liposome system
| Autor: | Kanji Takahashi, Nahoko Ogata, Rie Yamanaka, Mitsumasa Wada, Tsuyoshi Otsuji, Takashi Kimoto, Masanobu Uyama, Yasufumi Kaneda, Matsushima M |
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| Rok vydání: | 1999 |
| Předmět: |
Vascular Endothelial Growth Factor A
medicine.medical_specialty genetic structures VEGF receptors Confocal Rat model Genetic Vectors Endothelial Growth Factors Respirovirus Cellular and Molecular Neuroscience Rats Inbred BN medicine Animals Hvj liposome Fluorescent Dyes Liposome Drug Carriers Lymphokines Phosphorothioate Oligonucleotides biology Neovascularization Pathologic Oligonucleotide Chemistry Choroid Vascular Endothelial Growth Factors Gene Transfer Techniques Oligonucleotides Antisense Thionucleotides Molecular biology eye diseases Sensory Systems Surgery Rats Ophthalmology Choroidal neovascularization Liposomes biology.protein sense organs medicine.symptom Fluorescein-5-isothiocyanate |
| Zdroj: | Current eye research. 18(4) |
| ISSN: | 0271-3683 |
| Popis: | The purpose of this study was to determine whether the inactivated hemagglutinating virus of Japan (HVJ)-liposome method can induce phosphorothioate oligonucleotides effectively into an experimentally-induced choroidal neovascularization of rats. We also examined whether antisense phosphorothioate oligonucleotides against VEGF could be induced into choroidal neovascularization as a therapeutic agent by the HVJ-liposome method.The experiments were conducted on a rat model of choroidal neovascularization. FITC-labeled phosphorothioate oligonucleotides were coencapsulated in liposomes. The liposomes were coated with the envelope of inactivated HVJ and injected into the vitreous cavity following photocoagulation of pigmented rat eyes. The eyes were removed following injection, fixed, frozen and cut into thin sections. Induction of oligonucleotides was observed under a laser confocal scanning microscope for fluorescence and the development of choroidal neovascularization was evaluated histopathologically.Phosphorothioate oligonucleotides were effectively induced into ganglion cells and into the cells of the choroidal neovascularization induced by laser photocoagulation. Highly effective induction of oligos was observed 3 to 14 days after intravitreal injection of HVJ-liposomes after which the level decreased. Antisense oligonucleotides against VEGF were induced specifically into cells in the choroidal neovascularization, however neovascularization was still observed.Phosphorothioate oligonucleotides can be effectively induced into ganglion cells, and specifically into cells in choroidal neovascularization. Although antisense oligonucleotides against VEGF failed to prevent choroidal neovascularization, the HVJ-liposome method provided a highly effective means of inducing antisense oligos for in vivo antisense therapy. |
| Databáze: | OpenAIRE |
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