Inhibition of experimental choroidal neovascularization by overexpression of tissue inhibitor of metalloproteinases-3 in retinal pigment epithelium cells

被引：58

作者：

Takahashi, T

Nakamura, T

Hayashi, A

Kamei, M

Nakabayashi, M

Okada, AA

Tomita, N

Kaneda, Y

Tano, Y

机构：

[1] Osaka Univ, Sch Med, Dept Ophthalmol, Osaka, Japan

[2] Osaka Univ, Sch Med, Div Gene Therapy Sci, Osaka, Japan

[3] Osaka Univ, Sch Med, Dept Geriatr Med, Osaka 553, Japan

来源：

AMERICAN JOURNAL OF OPHTHALMOLOGY | 2000年 / 130卷 / 06期

关键词：

D O I：

10.1016/S0002-9394(00)00772-8

中图分类号：

R77 [眼科学];

学科分类号：

100212 ;

摘要：

PURPOSE: To evaluate the feasibility of introducing exogenous tissue inhibitor of metalloproteinases-3 gene into the rat retinal pigment epithelium using hemagglutinating virus of Japan liposomes and to assess the effect of tissue inhibitor of metalloproteinases-3 overexpression in retinal pigment epithelium cells on the formation of experimental choroidal neovascularization. METHODS: Hemagglutinating virus of Japan liposomes containing hemagglutin epitope-tagged tissue inhibitor of metalloproreinases-3 gene were injected into the subretinal space in rat eyes. Localization of oligonucleotides was evaluated by fluorescence microscopy. Exogenous tissue inhibitor of metalloproteinases-3 mRNA expression was assessed by reverse transcribed polymerase chain reaction. Exogenous tissue inhibitor of metalloproteinases-3 protein expression was visualized by immunostaining with monoclonal antibody 12CA5 against the hemagglutin epitope. Three days after transfection of tissue inhibitor of metalloproteinases-3 gene into retinal pigment epithelium cells, intense laser photocoagulation was performed and the incidence of: choroidal neovascularization was assessed by fluorescein fundus angiography. RESULTS: Exogenous tissue inhibitor of metalloproteinases-3 mRNA expression in the choroid and retina was detected on day 3. The efficiency of tissue inhibitor of metalloproteinases-3 gene transfection into retinal pigment epithelium cells was greatest on day 7 and decreased gradually thereafter. The incidence of choroidal neovascularization in tissue inhibitor of metalloproteinases-3 gene-transfected eyes was markedly decreased compared with controls. CONCLUSIONS: This study shows that tissue inhibitor of metaUoproteinases-3 gene can be transferred into rat retinal pigment epithelium using the hemagglutinating virus of Japan-liposome method and that tissue inhibitor of metalloproteinases-3 gene overexpression can inhibit development of experimental choroidal neovascularization. This method may represent a future treatment modality for human macular degeneration associated with choroidal neovascularization. (C) 2000 by Elsevier Science Inc. All rights reserved.

引用

页码：774 / 781

页数：8

共 39 条

[31] Development and characterization of cationic liposomes conjugated with HVJ (Sendai virus): Reciprocal effect of cationic lipid for in vitro and in vivo gene transfer [J].