Journal
ENEURO
Volume 4, Issue 1, Pages -Publisher
SOC NEUROSCIENCE
DOI: 10.1523/ENEURO.0331-16.2016
Keywords
brain-derived neurotrophic factor (BDNF); in vivo imaging; neuroprotection; optic nerve crush; retinal ganglion cells (RGCs)
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Funding
- National Institutes of Health (NIH) [R01EY026286]
- BrightFocus Foundation
- Northwestern Memorial Foundation
- Research to Prevent Blindness (Department of Ophthalmology)
- National Natural Science Foundation of China (NSFC) [31471054]
- Program of Introducing Talents of Discipline to Universities [B08020]
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Brain-derived neurotrophic factor (BDNF), a neurotrophin essential for neuron survival and function, plays an important role in neuroprotection during neurodegenerative diseases. In this study, we examined whether a modest increase of retinal BDNF promotes retinal ganglion cell (RGC) survival after acute injury of the optic nerve in mice. We adopted an inducible Cre-recombinase transgenic system to up-regulate BDNF in the mouse retina and then examined RGC survival after optic nerve crush by in vivo imaging. We focused on one subtype of RGC with large soma expressing yellow fluorescent protein transgene that accounts for similar to 11% of the total SMI-32-positive RGCs. The median survival time of this subgroup of SMI-32 cells was 1 week after nerve injury in control mice but 2 weeks when BDNF was up-regulated. Interestingly, we found that the survival time for RGCs taken as a whole was 2 weeks, suggesting that these large-soma RGCs are especially vulnerable to optic nerve crush injury. We also studied changes in axon number using confocal imaging, confirming first the progressive loss reported previously for wild-type mice and demonstrating that BDNF up-regulation extended axon survival. Together, our results demonstrate that the time course of RGC loss induced by optic nerve injury is type specific and that overexpression of BDNF prolongs the survival of one subgroup of SMI-32-positive RGCs. Key words: brain-derived neurotrophic factor (BDNF); in vivo imaging; neuroprotection; optic nerve crush; retinal ganglion cells (RGCs)
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