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Long-Term Protection of Retinal Ganglion Cells and Visual Function by Brain-Derived Neurotrophic Factor in Mice With Ocular Hypertension.
Invest Ophthalmol Vis Sci. 2016 07 01; 57(8):3793-802.IO

Abstract

PURPOSE

Glaucoma, frequently associated with elevated intraocular pressure (IOP), is characterized by progressive retinal ganglion cell (RGC) death and vision loss. Brain-derived neurotrophic factor (BDNF) has been studied as a candidate for neuroprotection in rodent models of experimental glaucoma, yet it remains to be determined whether BDNF exerts long-term protection for subtype RGCs and vision against chronic IOP elevation.

METHODS

We induced modest and sustained IOP elevation by laser illumination and microbead injection in mice. Using a tamoxifen-induced Cre recombinase system, BDNF was upregulated in the mouse retina when sustained IOP elevation was induced. We then examined whether overexpression of BDNF protected RGCs and vision during the period of ocular hypertension. Given that BDNF modulates axon growth and dendritic formation in a subtype-dependent manner, we tested whether BDNF protects RGC dendritic structure against the hypertensive insult also in a subtype-dependent manner.

RESULTS

Sustained IOP elevation was induced and lasted up to 6 months. Overexpression of BDNF delayed progressive RGC and axon loss in hypertensive eyes. Brain-derived neurotrophic factor overexpression also helped to preserve acuity against the chronic hypertensive insult. We classified RGCs into ON and ON-OFF subtypes based on their dendritic lamination pattern in the inner plexiform layer and found that BDNF prevented ON-RGC dendritic degeneration in mice with sustained ocular hypertension.

CONCLUSIONS

Our data demonstrated that BDNF can protect the dendritic fields of ON RGCs and reduce RGC and vision loss in mice with sustained ocular hypertension.

Authors+Show Affiliations

Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States 2Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, Illinois, United States.Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States.Department of Biomedical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University, Evanston, Illinois, United States.Department of Biomedical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University, Evanston, Illinois, United States.Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States 3Department of Biomedical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University, Evanston, Il.Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States 2Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, Illinois, United States.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27421068

Citation

Feng, Liang, et al. "Long-Term Protection of Retinal Ganglion Cells and Visual Function By Brain-Derived Neurotrophic Factor in Mice With Ocular Hypertension." Investigative Ophthalmology & Visual Science, vol. 57, no. 8, 2016, pp. 3793-802.
Feng L, Chen H, Yi J, et al. Long-Term Protection of Retinal Ganglion Cells and Visual Function by Brain-Derived Neurotrophic Factor in Mice With Ocular Hypertension. Invest Ophthalmol Vis Sci. 2016;57(8):3793-802.
Feng, L., Chen, H., Yi, J., Troy, J. B., Zhang, H. F., & Liu, X. (2016). Long-Term Protection of Retinal Ganglion Cells and Visual Function by Brain-Derived Neurotrophic Factor in Mice With Ocular Hypertension. Investigative Ophthalmology & Visual Science, 57(8), 3793-802. https://doi.org/10.1167/iovs.16-19825
Feng L, et al. Long-Term Protection of Retinal Ganglion Cells and Visual Function By Brain-Derived Neurotrophic Factor in Mice With Ocular Hypertension. Invest Ophthalmol Vis Sci. 2016 07 1;57(8):3793-802. PubMed PMID: 27421068.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long-Term Protection of Retinal Ganglion Cells and Visual Function by Brain-Derived Neurotrophic Factor in Mice With Ocular Hypertension. AU - Feng,Liang, AU - Chen,Hui, AU - Yi,Ji, AU - Troy,John B, AU - Zhang,Hao F, AU - Liu,Xiaorong, PY - 2016/7/16/entrez PY - 2016/7/16/pubmed PY - 2017/6/13/medline SP - 3793 EP - 802 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 57 IS - 8 N2 - PURPOSE: Glaucoma, frequently associated with elevated intraocular pressure (IOP), is characterized by progressive retinal ganglion cell (RGC) death and vision loss. Brain-derived neurotrophic factor (BDNF) has been studied as a candidate for neuroprotection in rodent models of experimental glaucoma, yet it remains to be determined whether BDNF exerts long-term protection for subtype RGCs and vision against chronic IOP elevation. METHODS: We induced modest and sustained IOP elevation by laser illumination and microbead injection in mice. Using a tamoxifen-induced Cre recombinase system, BDNF was upregulated in the mouse retina when sustained IOP elevation was induced. We then examined whether overexpression of BDNF protected RGCs and vision during the period of ocular hypertension. Given that BDNF modulates axon growth and dendritic formation in a subtype-dependent manner, we tested whether BDNF protects RGC dendritic structure against the hypertensive insult also in a subtype-dependent manner. RESULTS: Sustained IOP elevation was induced and lasted up to 6 months. Overexpression of BDNF delayed progressive RGC and axon loss in hypertensive eyes. Brain-derived neurotrophic factor overexpression also helped to preserve acuity against the chronic hypertensive insult. We classified RGCs into ON and ON-OFF subtypes based on their dendritic lamination pattern in the inner plexiform layer and found that BDNF prevented ON-RGC dendritic degeneration in mice with sustained ocular hypertension. CONCLUSIONS: Our data demonstrated that BDNF can protect the dendritic fields of ON RGCs and reduce RGC and vision loss in mice with sustained ocular hypertension. SN - 1552-5783 UR - https://www.unboundmedicine.com/medline/citation/27421068/Long_Term_Protection_of_Retinal_Ganglion_Cells_and_Visual_Function_by_Brain_Derived_Neurotrophic_Factor_in_Mice_With_Ocular_Hypertension_ L2 - https://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.16-19825 DB - PRIME DP - Unbound Medicine ER -