Budget Amount *help |
¥99,450,000 (Direct Cost: ¥76,500,000、Indirect Cost: ¥22,950,000)
Fiscal Year 2014: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2013: ¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2012: ¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
Fiscal Year 2011: ¥20,150,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥4,650,000)
Fiscal Year 2010: ¥24,180,000 (Direct Cost: ¥18,600,000、Indirect Cost: ¥5,580,000)
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Outline of Final Research Achievements |
During development, neurons guide and attract blood vessels and consequently the parallelism of these two is established. Here we identified a non-canonical neurovascular interaction in eye development. VEGFR2, a critical endothelial receptor for VEGF, was more abundantly expressed in retinal neurons than in endothelial cells including endothelial tip cells. Genetic deletion of VEGFR2 in neurons caused misdirected angiogenesis toward neurons resulting in abnormally increased vascular density around neurons. Further genetic experiments revealed that this misdirected angiogenesis was attributable to an excessive amount of VEGF protein around neurons caused by insufficient engulfment of VEGF by VEGFR2-deficient neurons. Moreover, absence of neuronal VEGFR2 caused misdirected regenerative angiogenesis in ischemic retinopathy. Thus, this study revealed novel neurovascular crosstalk and unprecedented cellular regulation of VEGF: retinal neurons titrate VEGF to limit neuronal vascularization.
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