Neurturin-mediated ret activation is required for retinal function

Milam A. Brantley, Sanjay Jain, Emily E. Barr, Eugene M. Johnson, Jeffrey Milbrandt

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

The glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) [GDNF, NRTN (neurturin), ARTN (artemin), and PSPN (persephin)] interact with GDNF family receptors (GFRαs) and activate intracellular signaling through the Ret receptor tyrosine kinase. To characterize the role of Ret signaling in retinal activity, we examined Ret hypomorphic and Ret conditional mice using electroretinography. We found that aberrant Ret function resulted in markedly diminished scotopic and photopic responses. Using mice deficient in individual GFLs, we found that only NRTN deficiency led to reduced retinal activity. To determine the potential target cell type for NRTN, we examined the retinal expression of its coreceptors (GFRα1 and GFRα2) and Ret using mice expressing fluorescence reporter enhanced green fluorescent protein from their respective loci. We found robust GFRα1 and Ret expression in horizontal, amacrine, and ganglion cells, whereas GFRα2 expression was only detected in a subset of amacrine and ganglion cells. In contrast to previous studies, no expression of GFRα1, GFRα2, or Ret was detected in photoreceptors or Müller cells, suggesting that these cells are not directly affected by Ret. Finally, detailed morphologic analyses of retinas from NRTN-and Ret-deficient mice demonstrated a reduction in normal horizontal cell dendrites and axons, abnormal extensions of horizontal cell and bipolar cell processes into the outer nuclear layer, and mislocalized synaptic complexes. These anatomic abnormalities indicate a possible basis for the abnormal retinal activity in the Ret and NRTN mutant mice.

Original languageEnglish
Pages (from-to)4123-4135
Number of pages13
JournalJournal of Neuroscience
Volume28
Issue number16
DOIs
StatePublished - Apr 16 2008

Keywords

  • ERG
  • Horizontal
  • Neurturin
  • Outer plexiform layer
  • RET
  • Retina

Fingerprint Dive into the research topics of 'Neurturin-mediated ret activation is required for retinal function'. Together they form a unique fingerprint.

  • Cite this