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

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.

• Authors: Godwin Okoye, Joelle Zimmer, Jennifer Sung, Peter Gehlbach, Tye Deering, Hiroyuki Nambu, Sean Hackett, Michele Melia, Noriko Esumi, Donald J Zack, Peter A Campochiaro
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 23 Issue 10 Pg. 4164-72 (May 15 2003) ISSN: 1529-2401 [Electronic] United States
• PMID: 12764104 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Brain-Derived Neurotrophic Factor
• Nerve Growth Factors
• RNA, Messenger
• Rhodopsin
• Doxycycline
• Oxygen

Topics

• Animals
• Brain-Derived Neurotrophic Factor (biosynthesis, deficiency, genetics)
• Cell Death (genetics, physiology)
• Cell Survival (genetics)
• Disease Models, Animal
• Doxycycline (pharmacology)
• Gene Expression Regulation (drug effects)
• Gene Transfer Techniques
• Hyperoxia (complications)
• Immunohistochemistry
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Mutation
• Nerve Growth Factors
• Oxygen (pharmacology)
• Photoreceptor Cells (injuries, metabolism)
• RNA, Messenger (biosynthesis)
• Rats
• Retina (chemistry, drug effects, metabolism, physiology)
• Retinal Degeneration (genetics, therapy)
• Rhodopsin (genetics, physiology)