1993 Fiscal Year Final Research Report Summary
Development of anti-after-cataract drug
| Project/Area Number |
03454414
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Ophthalmology
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| Research Institution | Osaka University |
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Principal Investigator |
KIRITOSHI Akira Osaka University, Ophthalmology, Assist-Prof., 医学部, 助手 (10225104)
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| Co-Investigator(Kenkyū-buntansha) |
KISHIDA Kenichi Osaka University, Ophthalmology, Prof., 医学部, 講師 (80028563)
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| Project Period (FY) |
1991 – 1993
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| Keywords | after-cataract / RGDS / cell adhesion factor / inhibitory factor of cell adhesion / lens epithelium / fibronectin |
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| Research Abstract |
・Our study strongly suggests that fibronectin has a key role in the attachment of lens epithelial cells. Arg-Gly-Asp-Ser(RGDS), a cell binding domain of fibronectin, was studied as an inhibitory factor to the adhesion of lens epithelial cells to develop an anti-after-cataract drug. We eatablished the chemical method to synthesize the RGDS tetramer.
・Arg-Gly-Asp-Ser(RGDS) inhibits the attachment of the cultured lens epithelial cell when added to the culture medium and co-incubated with the cells for 24 hours. The inhibitory effest was observed strongly in RGDS oligomer than in monom er. Both RGDS had no cytotoxic activity to cultured lens epithelial cells.
・From these results, it is suggested that 200-300 mug/ml of RGDS should be needed to investigate the inhibitory effect of RGDS in vivo experiments. By the reason of expence of RGDS, RGDS monomer was used for following in vivo experiments.
・After Japanese white rabbits' lens were extracted by ECCE technique, the migration of lens epithelial cells, those cause the after-cataract, were investigated by light-microscope on 7 and 14 days after lens extraction. In most samples, the lens epithelial cells migration to the center of posterior lens capsule was observed.
・Using this animal model, the inhibitory effects of RGDS was investigated. RGDS was dropped in slow-release copolymer pellet that attaced to intraocular lens and ECCE with IOL implantaion surgery were performed with rabbits. 10 days after surgery, eye balls were isolated and fixed for observation light-microscopically. The inhibitory effect of RGDS to migration of lens epithelial cells was oberved but did not make significant difference statistically becase of low number of vehicles. Further investigation will be needed for clinical use of RGDS.In addition, the effects of RGDS to corneal endothlium should be investigated to avoid the side effect of RGDS in human ocular tissue.
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