Reconnecting Eye to Brain

Abstract

Although much is known about the regenerative capacity of retinal ganglion cells, very significant barriers remain in our ability to restore visual function following traumatic injury or disease-induced degeneration. Here we summarize our current understanding of the factors regulating axon guidance and target engagement in regenerating axons, and review the state of the field of neural regeneration, focusing on the visual system and highlighting studies using other model systems that can inform analysis of visual system regeneration. This overview is motivated by a Society for Neuroscience Satellite meeting, "Reconnecting Neurons in the Visual System," held in October 2015 sponsored by the National Eye Institute as part of their "Audacious Goals Initiative" and co-organized by Carol Mason (Columbia University) and Michael Crair (Yale University). The collective wisdom of the conference participants pointed to important gaps in our knowledge and barriers to progress in promoting the restoration of visual system function. This article is thus a summary of our existing understanding of visual system regeneration and provides a blueprint for future progress in the field.

Keywords: axon; axon guidance; axon regeneration; eye; lateral geniculate nucleus; optic nerve; regeneration; retina; retinal ganglion cells; superior colliculus; traumatic brain injury; vision; visual cortex.

Figure 1.

RGCs encounter a number of barriers to regeneration following injury or trauma. In the eye, a range of factors, including cell-intrinsic transcription factors and receptors as well as exogenous growth factors, influence RGC survival and the ability of cells to generate axons and grow out of the eye and into the optic nerve. Some classes of RGCs show greater regenerative ability than others. In the optic nerve, supportive glia may not be present in the adult, and inhibitory influences associated with the scar block regeneration (blue axon). At the optic chiasm, growth cones are often misrouted toward the hypothalamus (green axons), or grow back into the opposite optic nerve, or halt completely. In the LGN and SC, if axon guidance factors are sufficient to guide the axons to these targets, synapses may form in the wrong retinotopic area, layer, or target cell. Synapse strength may also be inappropriate to mediate functional connections. In the visual cortex (and to a certain degree in the SC and LGN), regenerated connections may be too few or too weak, and circuit plasticity may not be adequate to compensate to generate useful functional response.