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J.A. Murphy, T.B. Franklin, D.B. Clarke; Brain–Derived Neurotrophic Factor Signaling Is Altered in the Visual System of Mice Deficient in the Neural Cell Adhesion Molecule . Invest. Ophthalmol. Vis. Sci. 2005;46(13):159.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Retinal ganglion cells (RGCs) in the adult mammalian retina degenerate and die by apoptosis in a predictable, time–dependent manner. Studies in culture suggest that signaling of brain derived neurotrophic factor (BDNF), a potent neurotrophic factor for RGCs, may be modulated by the neural cell adhesion molecule (NCAM). We have recently reported that in NCAM –/– mice, RGC densities are increased and the onset of injury–induced RGC loss is earlier. The goal of this project was to determine if these differences in RGC densities are due to altered trkB phosphorylation, and thus BDNF signaling, in NCAM –/– mice. Methods: To investigate BDNF signaling in the normal visual system of adult wild–type and NCAM –/– mice, tissue from retinas and superior colliculi was collected. BDNF levels were determined with ELISA, trkB levels were assessed by SDS–PAGE western blot analysis, and phosphorylated trkB was determined by immuno–precipitation followed by SDS–PAGE western blot analysis. Results: In the superior colliculi of NCAM –/– mice, BDNF levels were significantly higher and trkBTruncated levels were significantly lower compared to wild–type mice. However, trkB phosphorylation was not altered in the superior colliculi of NCAM –/– mice. In the retinas of NCAM –/– mice, no difference was found in BDNF levels; however, trkB phosphorylation was significantly higher as compared to wild–type retinas. Conclusions: Normal trkB phosphorylation in the superior colliculi of NCAM –/– mice, despite increased BDNF and decreased trkBTruncated, suggest that NCAM mediates BDNF signaling. In addition, the enhanced trkB–phosphorylation in the retinas of NCAM –/– mice may influence RGC densities in these mice.
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