Inhibition of experimental choroidal neovacularization by overexpreion of tiue inhibitor of metalloproteinae-3 in retinal pigment epithelium cell

PURPOE: To evaluate the feaibility of introducing exogenou tiue inhibitor of metalloproteinae-3 gene into the rat retinal pigment epithelium uing hemagglutinating viru of Japan lipoome and to ae the effect of tiue inhibitor of metalloproteinae-3 overexpreion in retinal pigment epithelium cell on the formation of experimental choroidal neovacularization. METHOD: Hemagglutinating viru of Japan lipoome containing hemagglutin epitope–tagged tiue inhibitor of metalloproteinae-3 gene were injected into the ubretinal pace in rat eye. Localization of oligonucleotide wa evaluated by fluorecence microcopy. Exogenou tiue inhibitor of metalloproteinae-3 mRNA expreion wa aeed by revere trancribed polymerae chain reaction. Exogenou tiue inhibitor of metalloproteinae-3 protein expreion wa viualized by immunotaining with monoclonal antibody 12CA5 againt the hemagglutin epitope. Three day after tranfection of tiue inhibitor of metalloproteinae-3 gene into retinal pigment epithelium cell, intene laer photocoagulation wa performed and the incidence of choroidal neovacularization wa aeed by fluorecein fundu angiography. REULT: Exogenou tiue inhibitor of metalloproteinae-3 mRNA expreion in the choroid and retina wa detected on day 3. The efficiency of tiue inhibitor of metalloproteinae-3 gene tranfection into retinal pigment epithelium cell wa greatet on day 7 and decreaed gradually thereafter. The incidence of choroidal neovacularization in tiue inhibitor of metalloproteinae-3 gene–tranfected eye wa markedly decreaed compared with control. CONCLUION: Thi tudy how that tiue inhibitor of metalloproteinae-3 gene can be tranferred into rat retinal pigment epithelium uing the hemagglutinating viru of Japan–lipoome method and that tiue inhibitor of metalloproteinae-3 gene overexpreion can inhibit development of experimental choroidal neovacularization. Thi method may repreent a future treatment modality for human macular degeneration aociated with choroidal neovacularization.