March 2012
Volume 53, Issue 14
ARVO Annual Meeting Abstract  |   March 2012
Olfactomedin 1 Is A New Novel Ligand Of Nogo Receptor 1 In The Retinal Ganglion Cells
Author Affiliations & Notes
  • Naoki Nakaya
    National Eye Institute, Bethesda, Maryland
  • Afia Sultana
    National Eye Institute, Bethesda, Maryland
  • Stanislav I. Tomarev
    National Eye Institute, Bethesda, Maryland
  • Footnotes
    Commercial Relationships  Naoki Nakaya, None; Afia Sultana, None; Stanislav I. Tomarev, None
  • Footnotes
    Support  the Intramural Research Program of the National Eye Institute, NIH
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 3959. doi:
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      Naoki Nakaya, Afia Sultana, Stanislav I. Tomarev; Olfactomedin 1 Is A New Novel Ligand Of Nogo Receptor 1 In The Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3959.

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

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Purpose: : Olfactomedin 1 (Olfm1), also known as noelin and pancortin, is a secreted glycoprotein that is highly conserved in vertebrates. The functions of Olfm1 are largely unknown. Here, we investigated the expression pattern of the Olfm1 protein in the mouse retina and looked for membrane receptor proteins interacting with Olfm1.

Methods: : The distribution of Olfm1 and several retinal markers was investigated by immunofluorescent labeling using a confocal laser microscope. COS7 cells were transfected with plasmids encoding candidate membrane proteins and treated with conditioned medium produced by another batch of COS7 cells transiently transfected with the Olfm1-alkaline phosphatase (AP) fusion construct. After incubation at 4°C, cells were washed and bound Olfm1-AP was detected by adding AP substrate solution. Co-immunoprecipitation and immunofluorescence co-localization analyses were also used to confirm binding of Olfm1 to membrane proteins.

Results: : Expression of Olfm1 in the retina was first detected at postconception day 13. Olfm1 was found mainly in post mitotic cells in the retinal ganglion cell layer. In adult mouse retina, most of the Olfm1-producing cells were also located in the retinal ganglion cell layer. Olfm1 protein was also detected in the nerve fiber layer and throughout the optic nerve including the corresponding brain target regions. Among 38 candidate proteins tested by AP assay, only NOGO receptor 1 (NgR1) showed highly positive binding to Olfm1-AP. Other receptors tested, including NgR2 and NgR3 that are similar to NgR1, were completely negative in this assay. NgR1 and Olfm1 were co-localized in the ganglion cell layer and nerve fiber layer of the retina as judged by immunofluorescence. Binding of Olfm1 to NgR1 was more efficient than binding of the well-known ligand of NgR1, myelin associated glycoprotein, as judged by the intensity of AP-staining with corresponding conditioned media. Olfm1 without the olfactomedin domain interacted well with NgR1, while Olfm1 with a deletion in the N-terminal domain failed to bind. These results indicated that the N-terminal domain of Olfm1 is essential for NgR1 binding. Binding of Olfm1 and NgR1 was further confirmed by co-immunoprecipitation in cell culture.

Conclusions: : Results strongly suggest that Olfm1 is a ligand of NgR1 that may modify the function of NgR1 in retinal ganglion cell axon growth and regeneration.

Keywords: retinal development • ganglion cells • optic nerve 

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