| Project/Area Number |
17591835
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Kobe University |
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Principal Investigator |
NAKAMURA Makoto Kobe University, Graduate School of Medicine, Assistant Professor (80273788)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Hiroyuki Kobe University, Graduate School of Medicine, Assistant Professor (60335453)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,270,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | diabetic retinonathv / retinal ganglion cells / anontoss / neu roprotection / nitric oxide |
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| Research Abstract |
In order o investigate if nipradilol and latanoprost have anti-apoptotic effects in retinal ganglion cells (RGCs), apoptosis was induced in RGC-5 cells by withdrawing serum and in rat retina by inducing diabetes with streptozotocin (STZ) injection. Apoptosis was quantified by activated caspase-3 immunohistochemistry on retinal cryosection or terminal dUTP nick end labeling staining. Nipradilol and latanoprost acid suppressed apoptosis of RGC-5 cells with dose dependency (p=0.001), whereas desnitro-nipradilol did not. Inhibitor studies showed that the anti-apoptotic effects of nipradilol were protein kinase A and G-dependent, whereas those of latanoprost acid were MAPK-dependent. Transfection of dominant negative mutants of CREB also blocked the nipradilol rescue effect. When instilled for 5 days, both nipradilol and latanoprost reduced apoptotic cells in retinal ganglion cell layer of 4-week and 12-week diabetic retina than controls (p<0.05 and p<0.0001, respectively). Desnitro-nipradilol eye drops did not show any effects. Latanoprost eye drops significantly increased MAPR phosphorylation in rat retina .These results indicated that nipradilol and latanoprost rescue RGCs from apoptosis induced by diabetes through distinct intracellular signaling pathways
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