RT Journal Article
SR Electronic
T1 Increased Expression of Brain-Derived Neurotrophic Factor Preserves Retinal Function and Slows Cell Death from Rhodopsin Mutation or Oxidative Damage
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 4164
OP 4172
DO 10.1523/JNEUROSCI.23-10-04164.2003
VO 23
IS 10
A1 Godwin Okoye
A1 Joelle Zimmer
A1 Jennifer Sung
A1 Peter Gehlbach
A1 Tye Deering
A1 Hiroyuki Nambu
A1 Sean Hackett
A1 Michele Melia
A1 Noriko Esumi
A1 Donald J. Zack
A1 Peter A. Campochiaro
YR 2003
UL http://www.jneurosci.org/content/23/10/4164.abstract
AB 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.