Purchase this article with an account.
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.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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).
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.
This PDF is available to Subscribers Only