| Co-Investigator(Kenkyū-buntansha) |
OHGURO Hiroshi Hirosaki University, School of Medicine, associate professor, 医学部, 助教授 (30203748)
NAKAZAWA Mitsuru Hirosaki University, School of Medicine, professor, 医学部, 教授 (80180272)
MAMIYA Kazuhisa Hirosaki University, University Hospital, Instructor, 医学部附属病院, 助手 (60344610)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
Purpose : To study the effects of antiglaucoma eye drops on N-methyl-D-aspartate (NMDA)-induced retinal damage and ocular surface
Methods : Several antiglaucoma eye drops, β-blockers, α/β-blockers, an α_1-blocker, and α_2-agonist, and a prostaglandin derivative, were topically administrated to NMDA-treated rat eyes or non-treated rat eye, and the retinal thickness, the number of retrograde-labeled retinal ganglion cells (RGCs), the results of a cDNA microarray analysis, and the levels of matrix metalloprotease (MMP) and tissue inhibitor of matrix protease (TIMP) which regulate the metabolism of the extracellular matrix (ECM) were studied.
Results : Intravitreal administration of NMDA caused a significant decrease in the thickness of the retinal layers and induced upregulation of glial fibrillary protein (GFAP). Topical administration of β-blockers and a prostaglandin derivative showed almost no significant effects on retinal thickness, the number of RGCs, or expression of GFAP. In contrast, the α/β-blockers, the α_1-blocker, and the α_2-agonist showed preservation effects on retinal thickness and the the number of RGCs, and marked suppression of NMDA-induced upregulation of GFAP. Among 1101 genes related to cellular regulatory mechanisms, the expression of two genes, both for insulin-like growth factors, IGF-1 and ErbB3,was altered upon administration of the α/β-blockers, the α_1-blocker, and the α_2-agonist. In addition, topical administration of the α/β-blockers, the α_1-blocker, and the prostaglandin derivative induced upregulation of MMP and downregulation of TIMP of conjunctiva.
Conclusion : Our present study suggests that modulations of the α-adrenergic receptor, α_1-blocking, and α_2-stimulation, by antiglaucoma eye drops may cause beneficial effects on NMDA-induced retinal damage in the rat. Our results also suggests that the α/β-blockers, the α_1-blocker, and the prostaglandin derivative induce degradation of ECM, affcting filter surgery.
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