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J. A. Murphy, D. B. Clarke; Target Tissue Supports the Survival of Adult Retinal Ganglion Cells in NCAM -/- Mice. Invest. Ophthalmol. Vis. Sci. 2007;48(13):231.
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During postnatal development, a shift occurs in the relative effectiveness of target-derived versus local neurotrophic support for sustaining retinal ganglion cell (RGC) survival. Specifically, target-derived factors are critical for developmental RGC survival but have little or no influence on adult RGC survival. We recently reported that in adult NCAM -/- mice, RGC densities are greater and the onset of injury-induced RGC loss is earlier, results that are consistent with an incomplete maturation of the mechanisms that govern RGC survival. Therefore, we wanted to determine whether the target tissue of adult NCAM -/- mice influences RGC survival
To determine whether adult RGCs of NCAM -/- mice mimic neonatal RGCs’ dependence on target sources of neurotrophic support, we labeled RGCs with fluorogold, subsequently aspirated the left SC in adult wild-type and NCAM -/- mice, and then quantified RGC densities 28 days after the lesion.
In wild-type mice (n = 3), there were no significant differences in RGC densities in retinas contralateral (2922 ± 30) compared with RGC densities in retinas ipsilateral (2986 ± 132; P = 0.663) to the lesion. In contrast, RGC densities in NCAM -/- mice (n = 4) decreased significantly after removal of the target (contralateral) SC (3283 ± 68; P < 0.001), a 15.2% loss compared with RGC densities in ipsilateral NCAM -/- retinas (3871 ± 54).
In contrast to the wild-type retinal projection system, the RGC target tissue of NCAM -/- mice continues to influence the survival of at least some RGCs into adulthood. These findings suggest that NCAM plays a vital role in RGCs’ switch in neurotrophic dependence from target to local-derived support during retinal development.
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