摘要 |
Angiogenesis-modifying composition (A) containing at least one of a nucleic acid (I) from the gene encoding IRS-1 (insulin receptor substrate-1), or its complement or fragments, or a molecule (II) that inhibits expression of the nucleic acid, is new. - ACTIVITY : Ophthalmological; Antiarthritic; Antirheumatic; Antiinflammatory; Gynecological; Antipsoriatic; Cytostatic; Vasotropic; Hypotensive; Vulnerary; Antianginal; Cardiant; Osteopathic. Corneal wounds were made in rats as described in Invest. Ophthalmol. Vis. Sci., 39 (1998) 18, then the animals given a subconjunctival injection of a composition containing 60 MicroM of the oligonucleotide (3), antisense to the IRS-1 gene 5'-TATCCGGAGGGCTCGCCATGCTGCT (3) in buffered saline, every day from days 4 to 9. The animals were killed on day 10 and the degree of neovascularization determined by staining with fluorescein-dextran, photography under a fluorescent microscope and then the ratio of neovascularized surface to total corneal surface was calculated. This ratio was 0.6157 (n = 15) for treated animals, compared with 0.9552 (n = 9) for those injected with saline only and 0.9170 (n = 9) for untreated animals, indicating a statistically significant reduction in neovascularization caused by (3). Similar results were obtained by topical application of an ointment containing 200 MicroM (3). - MECHANISM OF ACTION : Antisense gene therapy. |