title: 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 byin vivoimaging. 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.
authors.affiliation: Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Liang
authors.identifier: 0000-0003-1562-1662
authors.initials: L
authors.lastname: Feng
authors.affiliation: Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Biomedical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University, Evanston, IL 60208, USA; School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Zhen
authors.identifier: 0000-0002-3396-0927
authors.initials: Z
authors.lastname: Puyang
authors.affiliation: Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: School of Biomedical Engineering, Shanghai Jiao Tong University , Shanghai 200240, China.
authors.forename: Peiji
authors.initials: P
authors.lastname: Liang
authors.affiliation: Department of Biomedical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University , Evanston, IL 60208, USA.
authors.forename: John B
authors.initials: JB
authors.lastname: Troy
authors.affiliation: Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Xiaorong
authors.identifier: 0000-0002-7655-6342
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002452:Cell Count; D048429:Cell Size; D002470:Cell Survival / Q000502:physiology; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008822:Mice, Transgenic; D000066829:Neuroprotection / Q000502:physiology*; D020221:Optic Nerve Injuries / Q000378:metabolism* / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000473:pathology*; D015854:Up-Regulation
chemical_list: D019208:Brain-Derived Neurotrophic Factor
keywords: brain-derived neurotrophic factor (BDNF); in vivo imaging; neuroprotection; optic nerve crush; retinal ganglion cells (RGCs)