Overexpression of Brain-Derived Neurotrophic Factor Protects Large Retinal Ganglion Cells After Optic Nerve Crush in Mice

Abstract

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 ∼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.

Angiopoietin-1 Knockout Mice as a Genetic Model of Open-Angle Glaucoma

“…After in vivo imaging, some animals were allowed to recover on a heating pad, and others were intracardially perfused and eyes enucleated for histological analysis. 14,15 After recovery, animals were allowed to rest for at least 1 week before undergoing visual acuity and IOP measurement.…”

Regenerative Potential of Carbon Monoxide in Adult Neural Circuits of the Central Nervous System

“…Upregulation of BDNF in mouse retina plays an important role in neuroprotection; enhanced RGC survival after optic nerve crush is shown by in vivo imaging [146]. Induced adult hippocampal neurogenesis via injected P7C3 (pool 7, compound 3), a compound that enhances NPC survival and BDNF restore cognition in a 5xFAD (five AD-linked mutations expressing human amyloid protein precursor and presenilin-1 transgenes) AD mouse model [100].…”

Models and treatments for traumatic optic neuropathy and demyelinating optic neuritis

“…In more detail, it has been shown that BDNF enhances RGC survival post‐injury (Chen & Weber, ). Moreover, when BDNF is overexpressed specifically in the retinal tissue, the SMI‐32+ large soma RGCs survival is promoted since these cells are more vulnerable to acute injury post‐ONC (Feng et al, ). Finally, the combination of BDNF and the free radical scavenger S‐PBN in a rat model of ON transection, showed an increase in RGC survival but not an improvement in long‐distance axon regeneration.…”