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Submitted on July 3, 2006
Revised on January 25, 2007
Accepted on January 29, 2007

Elongation of axons during regeneration involves retinal crystallin beta b-2 (crybb2)

Thomas Liedtke, Jens C. Schwamborn, Uwe Schroeer, and Solon Thanos

Experimental Ophthalmology, University Eye Hospital Muenster, Muenster 48149

Corresponding Author: solon{at}uni-muenster.de

Adult retinal ganglion cells (RGCs) can regenerate their axons in vitro. Using proteomics, we have discovered that the supernatants of cultured retinas contain isoforms of crystallins, with crystallin beta-b2 (crybb2) being clearly upregulated in the regenerating retina. Immunohistochemistry revealed the expression of crybb within the retina, including in filopodial protrusions and axons of RGCs. Cloning and overexpression of crybb2 in RGCs and hippocampal neurons increased axonogenesis, which in turn could be blocked with antibodies against beta crystallin. Conditioned medium from crybb2-transfected cell cultures also supported the growth of axons. Finally, real-time imaging of the uptake of GFP-tagged-crybb2 fusion protein showed that this protein becomes internalized. These data are the first to show that axonal regeneration is related to crybb2 movement. The results suggest that neuronal crystallins constitute a novel class of neurite-promoting factors that likely operate through an autocrine mechanism, and that they could be used in neurodegenerative diseases.


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