| Co-Investigator(Kenkyū-buntansha) |
TAKEUCHI Hirofumi Gifu Pharmaceutical University, School of Pharmaceutical Sciences, Professor, 薬学部, 教授 (50171616)
TABATA Yasuhiko Kyoto University, Institute for Frontier Medical Sciences, Department of Biomaterials, Field of Tissue Engineering, Professor, 再生医科学研究所, 教授 (50211371)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
We evaluated chitosan-coated lipid nanosphere (CS-LNS) as a new topical eye drop system which can target the posterior pole of the eye. First, we did topical treatment on eyes of albino rabbit with CS-LNS containing DiI dye. CS-non-coated LNS was served as control. 1 hour after eye drops, eyes were enucleated and accumulation of DiI was examined by confocal laser scanning microscopy. DiI significantly accumulated in conjunctiva, cornea and anterior sclera-choroid-retina, but less in posterior sclera-choroid-retina. Next, we used CS-LNS containing cyclosporine as a topical treatment on eyes of albino rabbit. 1 hour after eye drops, eyes were enucleated and concentration of cyclosporine in following parts of the eyes, conjunctiva, cornea, iris, aqueous humor, lens vitreous, anterior sclera-choroid-retina and posterior sclera-choroid-retina, was measured by HPLC. We found significant levels of cyclosporine in conjunctiva and cornea. In anterior sclera-choroid-retina, the concentration of
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the drug was relatively lower than that of in conjunctiva and cornea. In posterior segment of the eye, it was much less. In iris, aqueous humor, lens and vitreous, we could not detect cyclosporine. These results suggested that drug delivery pathway with using CS-LNS was from conjunctiva to sclera via tenon. Pathway through cornea might not be a main road. Our study demonstrated that CS-LNS can be a new topical delivery system targeting to the posterior segment of the eye.
To search a new targeting molecule for the treatment of intraocular inflammation, we investigated changes in gene expression of cytokines and chemokines and their receptors after systemic prednisolone treatment in experimental autoimmune uveoretinitis (EAU). Gene expression analysis was conducted with the cDNA microarray, which contains 117 individual transcripts encoding the genes of the cytokines and chemokines and their receptors (29 cytokines/34 cytokine receptors; 33 chemokines/21 chemokine receptors). Comparisons of expression between predonisolone-treated and placebo-treated EAU mice at each time point were performed. The genes were sorted into clusters based on expression profiles to clarify the gene regulation pattern after treatment. Hierarchical cluster analysis of the microarray demonstrated that gene expression changes in EAU after treatment showed four patterns: flat, mountain, large downhill, and small downhill. These findings may open a new avenue to identify new therapeutic targets in ocular inflammation. Less
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