May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
Retinal Degeneration in CNG Channel Deficient Mouse Lines
Author Affiliations & Notes
  • S. Michalakis
    Pharmazie–Pharmakologie für Naturwissenschaften, Ludwig–Maximilians–Universität München, Munich, Germany
  • S. Hüttl
    Pharmazie–Pharmakologie für Naturwissenschaften, Ludwig–Maximilians–Universität München, Munich, Germany
  • M.W. Seeliger
    Retinal Electrodiagnostics Research Group, University Eye Hospital Tuebingen, Tuebingen, Germany
  • H. Geiger
    Pharmazie–Pharmakologie für Naturwissenschaften, Ludwig–Maximilians–Universität München, Munich, Germany
  • S. Haverkamp
    Max Planck Institute for Brain Research, Frankfurt/Main, Germany
  • A. Gerstner
    Pharmazie–Pharmakologie für Naturwissenschaften, Ludwig–Maximilians–Universität München, Munich, Germany
  • M. Biel
    Pharmazie–Pharmakologie für Naturwissenschaften, Ludwig–Maximilians–Universität München, Munich, Germany
  • Footnotes
    Commercial Relationships  S. Michalakis, None; S. Hüttl, None; M.W. Seeliger, None; H. Geiger, None; S. Haverkamp, None; A. Gerstner, None; M. Biel, None.
  • Footnotes
    Support  DFG
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 1680. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      S. Michalakis, S. Hüttl, M.W. Seeliger, H. Geiger, S. Haverkamp, A. Gerstner, M. Biel; Retinal Degeneration in CNG Channel Deficient Mouse Lines . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1680.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Abstract: : Purpose: Cyclic nucleotide–gated (CNG) channels play a central role in visual transduction. The channels are heteromers consisting of homologous A and B subunits. In this study, we characterized the morphological, biochemical and functional consequences of the genetic deletion of the cone–specific CNGA3 and the rod–specific CNGB1 subunit. Methods: Retinas of wildtype and CNGA3–deficient (CNGA3–/–) or CNGB1–deficient (CNGB1–/–) mice were analyzed by immunohistochemistry, molecular biology, electron microscopy, and electroretinography. Results: Mice deficient for the cone–type CNGA3 subunit failed to transport opsins into cone outer segments and down–regulated proteins of the phototransduction cascade including the cone B subunit, CNGB3. CNGA3–deficient cones induced apoptosis and degenerated starting after the second postnatal week. Degeneration proceeded significantly faster in ventral than in dorsal retina. The loss of CNGA3 profoundly delayed the migration of cone somata during postnatal development. As a consequence, at the time of eye opening most CNGA3–/– cones revealed displaced somata localized close to or in the outer plexiform layer lacking a characteristic cone pedicle. CNGB1–/– mice did not contain substantial amounts of the rod A subunit, CNGA1, and revealed no rod mediated responses. Rod outer segments were shorter than in wildtype mice, but contained significant amounts of rhodopsin. The rods also showed a slow–progressing degeneration caused by apoptotic death and concurred by retinal gliosis. Cones were primarily unaffected and showed normal light responses up to six months, but they started to degenerate in later stages. Conclusions: Our result indicate that both A and B subunits are required for the formation of functional CNG channels in photoreceptors. In both rods and cones loss of CNG channels destroyed visual transduction. By contrast, cell morphology was affected differentially in both types of photoreceptors. Opsin targeting to outer segments was disturbed in CNGA3–/– cones, but was normal in CNGB1–/– rods. Both CNG channel–deficient mouse lines revealed apoptotic photoreceptor death concurred by retinal gliosis. Unlike in CNGB1–/– mice no significant secondary loss of photoreceptors was observed in the CNGA3–/– retina.

Keywords: ion channels • photoreceptors • degenerations/dystrophies 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×