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Regulation of rod phototransduction machinery by ciliary neurotrophic factor

Wen, Rong; Song, Ying; Kjellstrom, Sten LU ; Tanikawa, Atsuhiro; Liu, Yun; Li, Yiwen; Zhao, Lian; Bush, Ronald A; Laties, Alan M and Sieving, Paul A. (2006) In The Journal of neuroscience : the official journal of the Society for Neuroscience 26(52). p.30-13523
Abstract

Ciliary neurotrophic factor (CNTF) promotes photoreceptor survival but also suppresses electroretinogram (ERG) responses. This has caused concerns about whether CNTF is detrimental to the function of photoreceptors because it is considered to be a potential treatment for retinal degenerative disorders. Here we report that the suppression of ERG responses is attributable to negative regulation of the phototransduction machinery in rod photoreceptors. Intravitreal injection of recombinant human CNTF protein in rat results in a series of biochemical and morphological changes in rod photoreceptors. CNTF induces a decrease in rhodopsin expression and an increase in arrestin level. Morphologically, CNTF treatment causes a shortening of rod... (More)

Ciliary neurotrophic factor (CNTF) promotes photoreceptor survival but also suppresses electroretinogram (ERG) responses. This has caused concerns about whether CNTF is detrimental to the function of photoreceptors because it is considered to be a potential treatment for retinal degenerative disorders. Here we report that the suppression of ERG responses is attributable to negative regulation of the phototransduction machinery in rod photoreceptors. Intravitreal injection of recombinant human CNTF protein in rat results in a series of biochemical and morphological changes in rod photoreceptors. CNTF induces a decrease in rhodopsin expression and an increase in arrestin level. Morphologically, CNTF treatment causes a shortening of rod outer segments (ROS). All of these changes are fully reversible. The lower rhodopsin level and shortened ROS reduce the photon catch of rods. Less rhodopsin and more arrestin dramatically increase the arrestin-to-rhodopsin ratio so that more arrestin molecules are available to quench the photoexcited rhodopsin. The overall effect of CNTF is to negatively regulate the phototransduction machinery, which reduces the photoresponsiveness of rods, resulting in lower ERG amplitude at a given intensity of light stimulus. The CNTF-induced changes in rods are similar to those in light-induced photoreceptor plasticity. Whether CNTF-induced changes in rods are through the same mechanism that mediates light-induced photoreceptor plasticity remains to be answered.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Ciliary Neurotrophic Factor, Dark Adaptation, Electroretinography, Humans, Rats, Rats, Long-Evans, Retinal Rod Photoreceptor Cells, Vision, Ocular, Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't
in
The Journal of neuroscience : the official journal of the Society for Neuroscience
volume
26
issue
52
pages
8 pages
publisher
Society for Neuroscience
external identifiers
  • scopus:33845897620
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.4021-06.2006
language
English
LU publication?
no
id
94c1efe1-701b-4b3c-9644-620a0e8c943f
date added to LUP
2017-04-14 08:34:52
date last changed
2018-05-13 04:30:32
@article{94c1efe1-701b-4b3c-9644-620a0e8c943f,
  abstract     = {<p>Ciliary neurotrophic factor (CNTF) promotes photoreceptor survival but also suppresses electroretinogram (ERG) responses. This has caused concerns about whether CNTF is detrimental to the function of photoreceptors because it is considered to be a potential treatment for retinal degenerative disorders. Here we report that the suppression of ERG responses is attributable to negative regulation of the phototransduction machinery in rod photoreceptors. Intravitreal injection of recombinant human CNTF protein in rat results in a series of biochemical and morphological changes in rod photoreceptors. CNTF induces a decrease in rhodopsin expression and an increase in arrestin level. Morphologically, CNTF treatment causes a shortening of rod outer segments (ROS). All of these changes are fully reversible. The lower rhodopsin level and shortened ROS reduce the photon catch of rods. Less rhodopsin and more arrestin dramatically increase the arrestin-to-rhodopsin ratio so that more arrestin molecules are available to quench the photoexcited rhodopsin. The overall effect of CNTF is to negatively regulate the phototransduction machinery, which reduces the photoresponsiveness of rods, resulting in lower ERG amplitude at a given intensity of light stimulus. The CNTF-induced changes in rods are similar to those in light-induced photoreceptor plasticity. Whether CNTF-induced changes in rods are through the same mechanism that mediates light-induced photoreceptor plasticity remains to be answered.</p>},
  author       = {Wen, Rong and Song, Ying and Kjellstrom, Sten and Tanikawa, Atsuhiro and Liu, Yun and Li, Yiwen and Zhao, Lian and Bush, Ronald A and Laties, Alan M and Sieving, Paul A.},
  issn         = {1529-2401},
  keyword      = {Animals,Ciliary Neurotrophic Factor,Dark Adaptation,Electroretinography,Humans,Rats,Rats, Long-Evans,Retinal Rod Photoreceptor Cells,Vision, Ocular,Comparative Study,Journal Article,Research Support, N.I.H., Extramural,Research Support, N.I.H., Intramural,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {12},
  number       = {52},
  pages        = {30--13523},
  publisher    = {Society for Neuroscience},
  series       = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
  title        = {Regulation of rod phototransduction machinery by ciliary neurotrophic factor},
  url          = {http://dx.doi.org/10.1523/JNEUROSCI.4021-06.2006},
  volume       = {26},
  year         = {2006},
}