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

PURPOSE: To evaluate the feasibility of introducing exogenous tissue inhibi tor of metalloproteinases-3 gene into the rat retinal pigment epithelium us ing hemagglutinating virus of Japan liposomes and to assess the effect of t issue inhibitor of metalloproteinases-3 overexpression in retinal pigment e pithelium cells on the formation of experimental choroidal neovascularizati on. METHODS: Hemagglutinating virus of Japan liposomes containing hemagglutin e pitope-tagged tissue inhibitor of metalloproreinases-3 gene were injected i nto the subretinal space in rat eyes. Localization of oligonucleotides was evaluated by fluorescence microscopy. Exogenous tissue inhibitor of metallo proteinases-3 mRNA expression was assessed by reverse transcribed polymeras e chain reaction. Exogenous tissue inhibitor of metalloproteinases-3 protei n expression was visualized by immunostaining with monoclonal antibody 12CA 5 against the hemagglutin epitope. Three days after transfection of tissue inhibitor of metalloproteinases-3 gene into retinal pigment epithelium cell s, intense laser photocoagulation was performed and the incidence of: choro idal 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 ep ithelium cells was greatest on day 7 and decreased gradually thereafter. Th e incidence of choroidal neovascularization in tissue inhibitor of metallop roteinases-3 gene-transfected eyes was markedly decreased compared with con trols. CONCLUSIONS: This study shows that tissue inhibitor of metaUoproteinases-3 gene can be transferred into rat retinal pigment epithelium using the hemag glutinating virus of Japan-liposome method and that tissue inhibitor of met alloproteinases-3 gene overexpression can inhibit development of experiment al choroidal neovascularization. This method may represent a future treatme nt modality for human macular degeneration associated with choroidal neovas cularization. (C) 2000 by Elsevier Science Inc. All rights reserved.