Macular Degeneration: Takahashi T

Sato T, Kanda T, Iida T, Takahashi T, Kishi S, Hoshino Y. · Department of Ophthalmology, Gunma University School of Medicine, Gunma, Japan. · J Int Med Res. · Pubmed #14587307 No free full text.

Abstract: We carried out an immunohistochemical investigation of the choroidal neovascular membranes from 12 eyes surgically excised as a result of age-related macular degeneration (n = 6) or idiopathic choroidal neovascularization (n = 6). Immunohistochemical staining was performed with antibodies specific for basic transcriptional element binding protein-2, actin or smooth muscle cell 1. In all membranes, the endothelial cells and stromal components around the vessels were immunoreactive for expression of basic transcriptional element binding protein-2, while immunoreactive expression of actin and smooth muscle cell type 1 was found in the surrounding stromal cells. These results suggest that basic transcriptional element binding protein-2, a zinc finger transcription factor, may contribute to the establishment of the choroidal neovascularization observed in the pathogenesis of age-related macular degeneration and idiopathic choroidal neovascularization.

Takahashi T, Nakamura T, Hayashi A, Kamei M, Nakabayashi M, Okada AA, Tomita N, Kaneda Y, Tano Y. · Department of Ophthalmology, Osaka University Medical School, Osaka, Japan. · Am J Ophthalmol. · Pubmed #11124297 No free full text.

Abstract: 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 metalloproteinases-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 metalloproteinases-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.