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M. V. Almeida, N. J. Kunzevitzky, S. Li, M. Xiang, J. L. Goldberg; Foxn4 Is Required for Retinal Ganglion Cell Axon Growth to the Superior Colliculus. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5704.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal ganglion cells (RGCs) fail to regenerate after injury. We previously demonstrated that RGCs undergo a developmental loss of their intrinsic capacity for axon growth around the time of birth, and that amacrine cells can signal neonatal rat RGCs to undergo a loss of intrinsic axon growth ability. Here we ask whether amacrine cells are required for proper RGC axon growth in vivo.
We studied RGC axon growth in vivo in the Foxn4 knockout mouse, in which there are a reduced number of retinal amacrine cells. Anterograde and retrograde tracing of RGC axons, and immunostaining for retinal markers were used to monitor RGC axon growth through development. Specifically, we injected alexa fluor 594- and 488-conjugated cholera toxin B subunit intravitreally, from postnatal day 0 to postnatal day 6. We euthanized the animals after 6 hours, section the brain and compare the distribution of the optic nerve fibers through the optic chiasm to the superior colliculus between the wild type/heterozygous and the knockout mice.
We found that from P0 to P3 there is a dramatic decrease in the distribution of the optic nerve projections to the superior colliculus in foxn4 knockout mice. By P4-P6 this difference is no longer present. Immunostaining confirmed a decrease in amacrine cells.
Foxn4 expression is required for proper targeting of RGC axons in vivo. These findings suggest that amacrine cells are critical for proper RGC axon growth, and raise the possibility that the amacrine cell-RGC interaction regulates RGC regeneration later in the adult. Future experiments are aimed at characterizing this interaction and defining the pathway by which Foxn4 mediates RGC axon growth in vivo.
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