PMID- 12764104 OWN - NLM STAT- MEDLINE DCOM- 20030625 LR - 20200225 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 23 IP - 10 DP - 2003 May 15 TI - Increased expression of brain-derived neurotrophic factor preserves retinal function and slows cell death from rhodopsin mutation or oxidative damage. PG - 4164-72 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. FAU - Okoye, Godwin AU - Okoye G AD - Department of Ophthalmology, Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9277, USA. FAU - Zimmer, Joelle AU - Zimmer J FAU - Sung, Jennifer AU - Sung J FAU - Gehlbach, Peter AU - Gehlbach P FAU - Deering, Tye AU - Deering T FAU - Nambu, Hiroyuki AU - Nambu H FAU - Hackett, Sean AU - Hackett S FAU - Melia, Michele AU - Melia M FAU - Esumi, Noriko AU - Esumi N FAU - Zack, Donald J AU - Zack DJ FAU - Campochiaro, Peter A AU - Campochiaro PA LA - eng GR - EY05951/EY/NEI NIH HHS/United States GR - K08EY13420/EY/NEI NIH HHS/United States GR - K08 EY013420/EY/NEI NIH HHS/United States GR - R01 EY005951/EY/NEI NIH HHS/United States GR - P30 EY001765/EY/NEI NIH HHS/United States GR - P30EY1765/EY/NEI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Nerve Growth Factors) RN - 0 (RNA, Messenger) RN - 9009-81-8 (Rhodopsin) RN - N12000U13O (Doxycycline) RN - S88TT14065 (Oxygen) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*biosynthesis/deficiency/genetics MH - Cell Death/genetics/physiology MH - Cell Survival/genetics MH - Disease Models, Animal MH - Doxycycline/pharmacology MH - Gene Expression Regulation/drug effects MH - Gene Transfer Techniques MH - Hyperoxia/complications MH - Immunohistochemistry MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Mutation MH - Nerve Growth Factors MH - Oxygen/pharmacology MH - Photoreceptor Cells/injuries/metabolism MH - RNA, Messenger/biosynthesis MH - Rats MH - Retina/chemistry/drug effects/metabolism/physiology MH - Retinal Degeneration/genetics/therapy MH - Rhodopsin/*genetics/physiology PMC - PMC6741081 EDAT- 2003/05/24 05:00 MHDA- 2003/06/26 05:00 PMCR- 2003/11/15 CRDT- 2003/05/24 05:00 PHST- 2003/05/24 05:00 [pubmed] PHST- 2003/06/26 05:00 [medline] PHST- 2003/05/24 05:00 [entrez] PHST- 2003/11/15 00:00 [pmc-release] AID - 23/10/4164 [pii] AID - 10.1523/JNEUROSCI.23-10-04164.2003 [doi] PST - ppublish SO - J Neurosci. 2003 May 15;23(10):4164-72. doi: 10.1523/JNEUROSCI.23-10-04164.2003.