May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
Ret is Necessary for Normal Retinal Function in Mice
Author Affiliations & Notes
  • M.A. Brantley, Jr.
    Washington University School of Medicine, St Louis, MO
    Ophthalmology and Visual Sciences,
  • E.E. Barr
    Washington University School of Medicine, St Louis, MO
    Ophthalmology and Visual Sciences,
  • S. Jain
    Washington University School of Medicine, St Louis, MO
    Surgery,
  • J. Milbrandt
    Washington University School of Medicine, St Louis, MO
    Pathology,
  • Footnotes
    Commercial Relationships  M.A. Brantley, None; E.E. Barr, None; S. Jain, None; J. Milbrandt, None.
  • Footnotes
    Support  K08 EY016140 HIGHWIRE EXLINK_ID="47:5:3766:1" VALUE="EY016140" TYPEGUESS="GEN" /HIGHWIRE –01
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 3766. doi:
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      M.A. Brantley, Jr., E.E. Barr, S. Jain, J. Milbrandt; Ret is Necessary for Normal Retinal Function in Mice . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3766.

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

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Abstract

Purpose: : Neurotrophic factors such as glial cell line–derived neurotrophic factor (GDNF) have been shown to slow the rate of certain forms of retinal degeneration. Little is known, however, about the role of these factors in the normal retina. The GDNF family ligands (GFLs: GDNF, NRTN, ARTN, and PSPN), with their respective GDNF family receptors (GFRαs), activate intracellular signaling through the Ret tyrosine kinase. The purpose of this study is to phenotypically characterize Ret loss–of–function mutants to determine if Ret is critical to normal retinal development and maintenance.

Methods: : To overcome the perinatal lethality of Ret null mice and assess the importance of Ret signaling in retinal function, we utilized a dominant negative Ret mutant (RetDN) mouse that survives approximately three weeks and has significantly reduced Ret function. Full–field electroretinograms (ERGs) were recorded from P18 RetDN and wild–type mice to a light intensity response series under both scotopic and photopic conditions. Retinal morphology was evaluated by light microscopy on routine histologic preparations from P18 RetDN mice.

Results: : RetDN mice at P18 demonstrated normal retinal morphology by light microscopy, including normal outer nuclear layer and inner nuclear layer thickness. On ERG testing, P18 RetDN mice displayed significantly reduced scotopic and photopic b–wave amplitudes compared to age–matched wild–type controls (p<0.005).

Conclusions: : Abnormal ERGs in RetDN mice demonstrate that GFL–mediated Ret signaling is required for normal retinal function. Interestingly, there is no obvious anatomic phenotype in the RetDN mice. These functional phenotypes devoid of gross anatomic basis suggest that the retinal dysfunction in Ret mutants is caused by a more subtle structural abnormality or is physiologic rather than anatomic in basis.

Keywords: retinal development • electroretinography: non-clinical • anatomy 
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