PMID- 17525224
OWN - NLM
STAT- MEDLINE
DCOM- 20070702
LR  - 20181113
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 48
IP  - 6
DP  - 2007 Jun
TI  - Paradoxical role of BDNF: BDNF+/- retinas are protected against light 
      damage-mediated stress.
PG  - 2877-86
AB  - PURPOSE: Photoreceptors can be prevented from undergoing apoptosis in response to 
      constant light by the application of exogenous neuroprotective agents, including 
      brain-derived neurotrophic factor (BDNF). BDNF, however, cannot exert its effect 
      directly on photoreceptors because they do not express receptors for BDNF. It has 
      been proposed that BDNF released from Muller cells provides a feed-forward loop, 
      increasing ciliary neurotrophic factor (CNTF) and basic fibroblast growth factor 
      (bFGF) production in Muller cells, which may enhance photoreceptor survival. The 
      authors hypothesized that retinas with reduced BDNF levels in which the 
      BDNF-mediated release of neuroprotective signals is dampened are more susceptible 
      to light-induced photoreceptor degeneration. METHODS: Young adult BDNF+/+ and 
      BDNF+/- littermates (B6.129-BDNF(tm1-LT)) were analyzed. Retinal neurotrophin and 
      growth factor mRNA levels were determined by quantitative RT-PCR, photoreceptor 
      function was assessed through electroretinography, and survival was documented in 
      morphologic sections and in TUNEL assays. Oxidative stress was assayed by 
      measuring glutathione peroxidase activity. RESULTS: At baseline, BDNF+/- animals 
      had significantly increased levels of glial-derived neurotrophic factor (GDNF) 
      mRNA compared with their wild-type littermates. After light damage GDNF, CNTF, 
      and BDNF mRNA levels dropped 14- to 16-fold in the BDNF+/+ mice but remained 
      almost unchanged compared with baseline levels in the BDNF+/- mice. Preservation 
      of neurotrophin levels in BDNF+/- mice correlated with photoreceptor cell 
      survival, preservation of function, and reduced oxidative stress. CONCLUSIONS: 
      Contrary to the hypothesis, reducing BDNF levels resulted in photoreceptor 
      protection against light damage. Survival was paralleled by a reduction in 
      oxidative stress and the preservation of neurotrophin levels, suggesting that 
      chronic reduction of BDNF in the retina provides a level of preconditioning 
      against stress.
FAU - Wilson, R Brooks
AU  - Wilson RB
AD  - Department of Ophthalmology, Medical University of South Carolina, Charleston, 
      South Carolina 29425, USA.
FAU - Kunchithapautham, Kannan
AU  - Kunchithapautham K
FAU - Rohrer, Barbel
AU  - Rohrer B
LA  - eng
GR  - EY-13520/EY/NEI NIH HHS/United States
GR  - EY-14793/EY/NEI NIH HHS/United States
GR  - R24 EY014793/EY/NEI NIH HHS/United States
GR  - R01 EY013520-04S1/EY/NEI NIH HHS/United States
GR  - AG-23630/AG/NIA NIH HHS/United States
GR  - P01 AG023630-029001/AG/NIA NIH HHS/United States
GR  - P01 AG023630/AG/NIA NIH HHS/United States
GR  - R01 EY013520-04/EY/NEI NIH HHS/United States
GR  - R01 EY013520/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Ciliary Neurotrophic Factor)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (RNA, Messenger)
RN  - EC 1.11.1.9 (Glutathione Peroxidase)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*physiology
MH  - Cell Survival
MH  - Ciliary Neurotrophic Factor/genetics
MH  - Electroretinography
MH  - Female
MH  - Glial Cell Line-Derived Neurotrophic Factor/genetics
MH  - Glutathione Peroxidase/metabolism
MH  - In Situ Nick-End Labeling
MH  - Light/adverse effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Nerve Growth Factors/genetics
MH  - *Oxidative Stress
MH  - RNA, Messenger/metabolism
MH  - Radiation Injuries, Experimental/metabolism/pathology/*prevention & control
MH  - Retina/*radiation effects
MH  - Retinal Degeneration/metabolism/pathology/*prevention & control
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC1964504
MID - NIHMS24415
EDAT- 2007/05/26 09:00
MHDA- 2007/07/03 09:00
PMCR- 2008/06/01
CRDT- 2007/05/26 09:00
PHST- 2007/05/26 09:00 [pubmed]
PHST- 2007/07/03 09:00 [medline]
PHST- 2007/05/26 09:00 [entrez]
PHST- 2008/06/01 00:00 [pmc-release]
AID - 48/6/2877 [pii]
AID - 10.1167/iovs.06-1079 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2007 Jun;48(6):2877-86. doi: 10.1167/iovs.06-1079.