Myelin from Peripheral and Central Nervous System Is a Nonpermissive Substrate for Retinal Ganglion Cell Axons

Abstract

In the CNS of mammals axonal regeneration is limited by inhibitory influences of the glial and extracellular environment. Myelin-associated inhibitors of neurite growth as well as some properties of so called "reactive astrocytes" which make the environment nonpermissive for axonal growth contribute to the inhibitory nature of the mammalian CNS. In contrast, the PNS is supportive of regeneration and Schwann cell surfaces and Schwann-cell-derived extracellular matrix provide suitable substrates for regenerating axons in vivo and in vitro. However, as the results presented here indicate, myelin derived from normal and axotomized sciatic nerves is a nonpermissive substrate for axonal regrowth. Addition of laminin to either CNS or PNS myelin or freezing of the myelin, however, allows reproducibly axonal growth. Membrane preparations from CNS or PNS tissue on the other hand allow axon outgrowth from retinal explants when adhesive substrates (e.g., polylysin) are available. This suggests that inhibitors of neurite growth are present in myelin from the CNS and PNS. Growth supportive substrates, which are present in large quantities after PNS but not after CNS injury, can overcome nonpermissive substrate properties.