Long-term protection of retinal ganglion cells and visual function by brain-derived neurotrophic factor in mice with ocular hypertension

Liang Feng, Hui Chen, Ji Yi, John B. Troy, Hao F. Zhang, Xiaorong Liu*

*Corresponding author for this work

Research output: Contribution to journalArticle

20 Scopus citations

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 longterm 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.

Original languageEnglish (US)
Pages (from-to)3793-3802
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume57
Issue number8
DOIs
StatePublished - Jul 2016

Keywords

  • Brain-derived neurotrophic factor (BDNF)
  • Experimental glaucoma
  • Neuroprotection
  • Retinal ganglion cells (RGCs)
  • Visual acuity

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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