Polysialylated Neural Cell Adhesion Molecule Protects Against Light-Induced Retinal Degeneration.
OBJECTIVE
We previously demonstrated that neural cell adhesion molecule (NCAM) plays an important role in supporting the survival of injured retinal ganglion cells. In the current study, we used light-induced retinal degeneration (LIRD) as a model to investigate whether NCAM plays a functional role in neuroprotection and whether NCAM influences p75NTR signaling in modulating retinal cell survival.


METHODS
Retinas from wild-type (WT) and NCAM deficient (-/-) mice were tested by electroretinogram before and after LIRD, and changes in the protein expressions of NCAM, polysialic acid (PSA)-NCAM, p75NTR, and active caspase 3 were measured by immunoblot from 0 to 4 days after light induction. The effects of NCAM and PSA-NCAM on p75NTR were examined by intraocular injections of the p75NTR function-blocking antibody and/or the removal of PSA with endoneuraminidase-N prior to LIRD.


RESULTS
In WT mice, low levels of active caspase 3 activation were detected on the first day, followed by increases up to 4 days after LIRD. Conversely, in NCAM-/- mice, higher cleaved caspase 3 levels along with rapid reductions in electroretinogram amplitudes were found earlier at day 1, followed by reduced levels by day 4. The removal of PSA prior to LIRD induced earlier onset of retinal cell death, an effect delayed by the coadministration of endoneuraminidase-N and the p75NTR function-blocking antibody antiserum.


CONCLUSIONS
These results indicate that NCAM protects WT retinas from LIRD; furthermore, the protective effect of NCAM is, at least in part, attributed to its effects on p75NTR.
Department of Medical Neuroscience, Dalhousie University, Life Science Research Institute, Halifax, Nova Scotia, Canada.
Margaret Po-Shan
MP
Luke
Department of Medical Neuroscience, Dalhousie University, Life Science Research Institute, Halifax, Nova Scotia, Canada.
Terry L
TL
LeVatte
Cellular and Developmental Neuroscience, Department of Cell Biology, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York, United States.
Urs
U
Rutishauser
Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada 4Department of Ophthalmology & Visual Sciences, Dalhousie University, Halifax, Nova Scotia, Canada.
François
F
Tremblay
Department of Medical Neuroscience, Dalhousie University, Life Science Research Institute, Halifax, Nova Scotia, Canada 4Department of Ophthalmology & Visual Sciences, Dalhousie University, Halifax, Nova Scotia, Canada 5Department of Surgery (Neurosurgery), Dalhousie University, Halifax, Nova Scotia, Canada.
David B
DB
Clarke
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