| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Outline of Final Research Achievements |
Retinal ganglion cell (RGC) degeneration is believed to underlie many ocular diseases including glaucoma. In these diseases, RGCs are affected unevenly, both spatially and temporally, such that healthy and unhealthy RGCs coexist in different patterns at different time points. We describe a temporally and spatially regulated AAV gene therapy aiming to reduce undesired off-target effects on healthy RGCs. The Mcp-1 promoter shown to be transcribed in stressed RGCs following murine optic nerve injury was combined with the neuroprotective transcription factor NRF2. In this model, Mcp-1-driven NRF2 expression targeting only stressed RGCs showed efficacy equivalent to non-selective CMV promoter-driven therapy for preventing RGC death. However, CMV promoter-mediated NRF2 transcription induced cellular stress responses and death of uninjured RGCs. Combining a stress-responsive promoter and therapeutic gene is a versatile strategy for specifically targeting cells at risk of degeneration.
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