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Originally published In Press as doi:10.1167/iovs.08-2334 on August 29, 2008
 (Investigative Ophthalmology and Visual Science. 2009;50:861-869.)
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.08-2334
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Endogenous Polysialylated Neural Cell Adhesion Molecule Enhances the Survival of Retinal Ganglion Cells

Jeremy A. Murphy,1,2 Andrew T. E. Hartwick,2,3 Urs Rutishauser,4 and David B. Clarke1,2,5

1From the Neuron Survival and Regeneration Laboratory and the 2Departments of Anatomy & Neurobiology and 5Surgery (Neurosurgery), Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada; and 4Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, Program in Cell Biology, New York, New York.

PURPOSE. During development, all retinal cells express polysialylated neural cell adhesion molecule (PSA-NCAM). PSA is localized only on glia in the adult retina, but as Müller glial processes ensheathe most retinal neurons, PSA remains in the extracellular environment of adult neurons. The authors sought to investigate the influence of endogenous PSA on the survival of neonatal as well as adult normal and injured retinal ganglion cells (RGCs).

METHODS. Endogenous retinal PSA was selectively degraded by application of endoneuraminidase. PSA presence and removal were confirmed by immunohistochemistry and levels were assessed by Western Blot analysis. Neonatal RGC survival after PSA removal was assessed in vitro in RGCs immunopanned from rat pups. Adult RGC survival was assessed in vivo in mice by investigating RGC densities after removal of PSA in normal retinas and after optic nerve transection.

RESULTS. Virtually all neonatal RGCs express PSA-NCAM and survive well in vitro; however, removal of PSA resulted in a 42% loss of these cells 3 days after the treatment. Similarly, removal of PSA in the adult retina in vivo induced a loss of 25% of RGCs at 14 days, and significantly reduced RGC densities after optic nerve transection by an additional 27% (relative to injured retinas with a vehicle injection) at 7 days.

CONCLUSIONS. Together, these findings demonstrate that endogenous PSA supports the survival of neonatal as well as injured and normal adult RGCs and provide the first functional evidence of a role for PSA in the adult retina.






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