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Stimulating axonal regeneration of mature retinal ganglion cells and overcoming inhibitory signaling

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Abstract

Like other neurons of the central nervous system (CNS), retinal ganglion cells (RGCs) are normally unable to regenerate injured axons and instead undergo apoptotic cell death. This regenerative failure leads to lifelong visual deficits after optic nerve damage and is partially attributable to factors located in the inhibitory environment of the forming glial scar and myelin as well as to an insufficient intrinsic ability for axonal regrowth. In addition to its ophthalmological relevance, the optic nerve has long been used as a favorable paradigm for studying regenerative failure in the CNS as a whole. Findings over the last 15 years have shown that, under certain circumstances, mature RGCs can be transformed into an active regenerative state enabling these neurons to survive axotomy and to regenerate axons in the optic nerve. Moreover, combinatorial treatments overcoming the inhibitory environment of the glial scar and optic nerve myelin, together with approaches activating the intrinsic growth program, can further enhance the amount of regeneration in vivo. These findings are encouraging and open the possibility that clinically meaningful regeneration may become achievable in the future.

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Acknowledgments

I am grateful to Philipp Gobrecht, Marco Leibinger and Vetrivel Sengottuvel for critically reading the manuscript and for suggestions. I apologize to all colleagues whose important work is not included here because of space limitations.

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  1. Department of Neurology, Experimental Neurology, Heinrich Heine University Düsseldorf, Merowingerplatz 1a, 40225, Düsseldorf, Germany

    Dietmar Fischer

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Correspondence to Dietmar Fischer.

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This work was supported by the German Research Foundation.

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Fischer, D. Stimulating axonal regeneration of mature retinal ganglion cells and overcoming inhibitory signaling. Cell Tissue Res 349, 79–85 (2012). https://doi.org/10.1007/s00441-011-1302-7

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