Inactivation of myelin-associated glycoprotein enhances optic nerve regeneration.
CNS regeneration in higher vertebrates is a long sought after goal in neuroscience. The lack of regeneration is attributable in part to inhibitory factors found in myelin (Caroni and Schwab, 1988a). Myelin-associated glycoprotein (MAG) is an abundant myelin protein that inhibits neurite outgrowth in vitro (McKerracher et al., 1994; Mukhopadhyay et al., 1994), but its role in regeneration remains controversial. To address this role, we performed nerve crush on embryonic day 15 chick retina-optic nerve explants and then acutely eliminated MAG function along the nerve using chromophore-assisted laser inactivation (CALI). CALI of MAG permitted significant regrowth of retinal axons past the site of lesion containing CNS myelin in contrast to various control treatments. Electron microscopy of the site of nerve crush shows abundant regenerating axons crossing the gap. When crushed optic nerve was retrogradely labeled at the nerve stump, no labeling of retinal neurons was observed. In contrast, labeling of CALI of MAG-treated crushed optic nerve showed significant retinal labeling (89 +/- 16 cells per square millimeter), a value indistinguishable from that seen with non-crushed nerve (98 +/- 13 cells per square millimeter). These findings implicate MAG as an important component of the myelin-derived inhibition of nerve regeneration. The acute loss of MAG function can promote significant axon growth across a site of CNS nerve damage.
Wong
Eric V
EV
Department of Physiology, Tufts University Medical School, Boston, Massachusetts 02111, USA.
David
Samuel
S
Jacob
Michele H
MH
Jay
Daniel G
DG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D001369:Axons / Q000187:drug effects / Q000528:radiation effects / Q000648:ultrastructure; D002478:Cells, Cultured; D002642:Chick Embryo; D005456:Fluorescent Dyes; D005609:Free Radicals / Q000378:metabolism / Q000494:pharmacology; D020439:Growth Cones / Q000187:drug effects / Q000528:radiation effects / Q000648:ultrastructure; D007834:Lasers; D008027:Light; D009186:Myelin Sheath / Q000502:physiology; D018992:Myelin-Associated Glycoprotein / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000502:physiology* / Q000528:radiation effects; D009900:Optic Nerve / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D009924:Organ Culture Techniques; D010777:Photochemistry; D012160:Retina / Q000166:cytology / Q000196:embryology; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D012394:Rosaniline Dyes / Q000737:chemistry / Q000528:radiation effects
D000911:Antibodies, Monoclonal; D005456:Fluorescent Dyes; D005609:Free Radicals; D018992:Myelin-Associated Glycoprotein; D012394:Rosaniline Dyes; C005095:malachite green