2001 Fiscal Year Final Research Report Summary
Development of readily applicable glaucoma new drugs for lowering intraocular pressure, improvement of ocular circulation, and neuronprotection
| Project/Area Number |
11307036
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
ARAIE Makoto School of Medicine, Department of Ophthalmology, The University of Tokyo, Professor, 医学部・附属病院, 教授 (00092122)
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| Co-Investigator(Kenkyū-buntansha) |
KASHIWAGI Kenji Yamanashi Medical University, Lecturer, 医学部・附属病院・眼科, 講師 (30194723)
AMANO Shiro School of Medicine, Department of Ophthalmology, The University of Tokyo, Lecturer, 医学部・附属病院, 講師 (80193027)
SUZUKI Yasuyuki School of Medicine, Department of Ophthalmology, The University of Tokyo, Lecturer, 医学部・附属病院, 講師 (80196881)
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| Project Period (FY) |
1999 – 2001
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| Keywords | glaucoma / intraocular pressure reduction / optic nerve blood flow / retinal ganglion cell death / experimental glaucoma / neuroprotection / cultured retinal ganglion cell / glutamate |
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| Research Abstract |
The intraocular pressure lowering effect of a selective alpha1D adrenergic antagonist was studied. The selective alpha1D adrenergic antagonist was effective in increasing aqueous outflow in Dutch rabbit but not in cynomolgus monkey. The effect of this drug seemed to be different among species.
The role of Na^+-HCO_3 cotransporter (NBG-1) in ocular tissues was studied. Immunohistological analysis of human and rat ocular tissue was performed using specific anti-body of kidney-type NEC-1 and pancreas-type NBC-1. Both types were expressed in corneal epithelium, lens epithelium, and trabecular meshwork. NBC-1 was suggested to have some role in regulation of aqueous humor outflow.
The autoregulation function of optic nerve blood flow was studied using white rabbits. The optic nerve blood flow showed autoregulation in response to acute intraocular pressure increase or reduction. The function was attenuated by a Ca^<2+> blocker but not by a nitric oxide synthetase inhibitor, indomethacin, nor sympathetic denervation.
In vivo experiments using rat experimental glaucoma model or retinal ganglion cell damage model showed that a Ca^<2+> blocker had neuroprotective effect on the retinal ganglion cell damage caused by kainate.
Experiments using purely isolated rat retinal ganglion cell and glial cells showed that glial cells influence the survival of retinal ganglion cells. Hypoxic stress and high pressure stress induce the production of nitric oxide and suppress the expression of neurotrophic factors in glial cells.
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