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 following 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 following optic nerve crush by in vivo imaging. We focused on one subtype of RGC with large soma expressing yellow fluorescent protein (YFP) transgene, which accounts for about 11% of the total SMI-32 positive RGCs. The median survival time of this subgroup of SMI-32 cells was one week following nerve injury in control mice, but two weeks when BDNF was up-regulated. Interestingly, we found that the survival time for RGCs taken as a whole was two 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.
Significance Statement The primary goal of this study was to investigate the role of BDNF on RGC survival following optic nerve injury. We adopted an inducible Cre-recombinase transgenic system to modestly up-regulate BDNF in the mouse retina. We then applied a live imaging technique to track the survival of RGCs expressing yellow fluorescent protein (YFP) in vivo. We identified one type of RGC with a large soma which accounts for about 11% of the total SMI-32 positive RGCs. Our results showed that these cells were more susceptible to acute optic nerve injury. Furthermore, we found that BDNF up-regulation promoted survival of these large-soma SMI-32-positive RGCs. Our study thus adds new insights on better understanding of type-specific RGC loss post optic nerve injury and the underlying BDNF-mediated neuroprotective mechanism.
The authors declare no competing financial interests.
This work was supported by the National Institutes of Health (NIH) grant R01EY026286 (X.L.), and grants from the BrightFocus Foundation (L.F. and X.L.), Northwestern Memorial Foundation (X.L.), the Research to Prevent Blindness (Department of Ophthalmology), National Natural Science Foundation of China (P.L., NSFC No. 31471054), and the Program of Introducing Talents of Discipline to Universities (P.L., No. B08020).