RGD Reference Report - The repulsive guidance molecule, RGMa, promotes retinal ganglion cell survival in vitro and in vivo. - Rat Genome Database

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The repulsive guidance molecule, RGMa, promotes retinal ganglion cell survival in vitro and in vivo.

Authors: Koeberle, PD  Tura, A  Tassew, NG  Schlichter, LC  Monnier, PP 
Citation: Koeberle PD, etal., Neuroscience. 2010 Aug 11;169(1):495-504. doi: 10.1016/j.neuroscience.2010.04.079. Epub 2010 May 8.
RGD ID: 9850136
Pubmed: PMID:20457227   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neuroscience.2010.04.079   (Journal Full-text)

The repulsive guidance molecule, RGMa, and its receptor Neogenin, regulate neuronal cell death during development, but little is known about their expression and roles in the adult CNS. Here, we show that Neogenin is expressed in the adult rodent retina, particularly on retinal ganglion cells. To determine whether the Neogenin/RGMa pathway is important in the fully developed retina, we examined its contribution to damage-induced neurodegeneration. The effects of RGMa on survival of retinal ganglion cells (RGCs) were examined in vitro and in vivo. Using cultured whole-mount retinal explants, we showed that the addition of RGMa increased RGC survival and that this effect was mediated by the Neogenin receptor. Immunohistochemical analysis indicated that the inhibition of cell death by RGMa resulted from reduced caspase-3 activation. Then, using an in vivo model of RGC apoptosis after optic nerve transection, we demonstrated that intraocular injection of RGMa at 3 and 7 days after axotomy greatly reduced RGC death 14 days postaxotomy. This study provides the first evidence that RGMa is a molecular target for neuroprotection in retinal pathologies, and suggests that targeting "dependence receptors" such as Neogenin has therapeutic potential for the treatment of neuropathologies in the adult CNS.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Neo1Ratnegative regulation of cellular process  IMP retinal ganglion cellsRGD 

Cellular Component

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Neo1Ratneuronal cell body  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Neo1  (neogenin 1)

Additional Information