Increased expression of brain-derived neurotrophic factor preserves retinal function and slows cell death from rhodopsin mutation or oxidative damage

Godwin Okoye, Joelle Zimmer, Jennifer Sung, Peter Gehlbach, Tye Deering, Hiroyuki Nambu, Sean Hackett, Michele Melia, Noriko Esumi, Donald J Zack, Peter A Campochiaro

Research output: Contribution to journalArticle

Abstract

There are no effective treatments for inherited retinal degenerations, which are prevalent causes of visual disability. Several proteins promote the survival of various types of neurons, and increasing expression of one or more of these survival factors is a promising strategy for a new treatment. Studies examining the effects of intravitreous injections of brain-derived neurotrophic factor (BDNF) in models of inherited retinal degenerations have suggested that BDNF has little survival-promoting activity for photoreceptors. In this study, we generated double transgenic mice with doxycycline-inducible expression of BDNF in the retina. In a model of primary rod photoreceptor degeneration, expression of BDNF resulted in significant delay in photoreceptor cell death and maintenance of retinal function assessed by electroretinogram recordings. Expression of BDNF also caused strong protection of photoreceptors from oxidative damage-induced cell death. These data suggest that continuous expression of BDNF, unlike intravitreous injections, results in morphologic and functional benefit in animal models of inherited retinal degeneration. Double transgenic mice with inducible expression of survival factors provide valuable tools for selection of survival factor candidates for gene therapy.

Original languageEnglish (US)
Pages (from-to)4164-4172
Number of pages9
JournalJournal of Neuroscience
Volume23
Issue number10
StatePublished - May 15 2003

Fingerprint

Rhodopsin
Brain-Derived Neurotrophic Factor
Cell Death
Retinal Degeneration
Mutation
Transgenic Mice
Retinal Rod Photoreceptor Cells
Photoreceptor Cells
Injections
Doxycycline
Genetic Therapy
Retina
Animal Models
Maintenance
Neurons
Therapeutics
Proteins

Keywords

  • BDNF
  • Gene transfer
  • Inducible transgenics
  • Neurotrophic factors
  • Oxidative damage
  • Retinal degenerations

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Increased expression of brain-derived neurotrophic factor preserves retinal function and slows cell death from rhodopsin mutation or oxidative damage. / Okoye, Godwin; Zimmer, Joelle; Sung, Jennifer; Gehlbach, Peter; Deering, Tye; Nambu, Hiroyuki; Hackett, Sean; Melia, Michele; Esumi, Noriko; Zack, Donald J; Campochiaro, Peter A.

In: Journal of Neuroscience, Vol. 23, No. 10, 15.05.2003, p. 4164-4172.

Research output: Contribution to journalArticle

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