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P. Ekstrom, B. Holmqvist, T. van Veen, P. Alm; Distribution of Polysialic Acid - Neural Cell Adhesion Molecule (PSA-NCAM) in vivo and in vitro in Developing Retinas of Normal and rd Mice . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1611.
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Purpose: The adhesive action of the neural cell adhesion molecule (NCAM) is reduced after linkage of residues of polysialic acid (PSA), thus forming an extracellular complex (PSA-NCAM) with non-adhesive properties, known to play fundamental roles in neurogenesis and neural plasticity. To investigate if PSA-NCAM is involved in the retinogenesis and in the mechanisms of retinal degenerative diseases, we studied the expression of PSA-NCAM in early postnatal retinas from wild-type mice and from mice carrying the rd mutation, i.e. exhibiting photoreceptor degeneration. The investigation also included cultured retinas. Methods: Specimens consisted of retinas from C3H mice, with or without (WT) the rd mutation, sampled at various time points between postnatal day 1 (PN1) and PN28, and retinal explants that had been kept in vitro for 3 weeks from PN7. The preparations were fixed, cryosectioned and labelled with PSA antibodies. Specific recognition of the PSA-NCAM complex by the PSA antibodies was verified by double labelling with NCAM antibodies (obligatory colocalization) and by treatment with neuraminidases (abolished labelling). Results: PSA immunoreactivity (IR) of extracellular elements was detected in all retinas analysed, including in the cultured explants. The spatial pattern of PSA IR in the retinas changed with the state of development. At earlier time points (e.g. PN3) the labelling was homogenous and present throughout the whole retina, although a relatively more intense labelling was indicated in future ganglion cells (RGC) and inner nuclear layer (INL). With time the PSA IR became more diversified. At PN7-9 there was comparatively more PSA IR around INL cells than around photoreceptors and a clear stratification was present in the inner plexiform layer (IPL), with PSA IR almost exclusively in the strata 1, 3 and 5. The relatively intense PSA IR in RGC and nerve fibers and the stratified PSA IR in the IPL was retained in adult stages. In the optic nerve PSA IR was strong during the earlier time points studied only. Conclusions: PSA-NCAM is widely distributed in the retina after birth and the expression follows the morphogenesis of the retina of both WT and rd mice. The specific pattern established during neonatal development is kept in the adult animal. PSA-NCAM could thus participate in retinal formation as well as in retinal plasticity and function throughout life. The expression of the PSA-NCAM complex under in vitro conditions provides a basis for studies of its functional role in developmental and degenerative processes.
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