Numerous neurite growth-inhibitory molecules have been found to be upregulated on the surface of nonpermissive glial structures after injury to the CNS, as well as in the graft–host interface in brain cell transplantation, constituting a molecular barrier preventing graft-derived axons from entering the host.
15 16 17 18 19 20 43 44 57 58 59 In the spinal cord, especially chondroitin sulfate proteoglycans appear to contribute to the nonpermissive properties of the glial scar tissue, since it has been observed that treatment with chondroitinase, enzyme-digesting chondroitin sulfate chains, promotes regeneration of axons and even functional recovery.
60 An analysis of changes in the distribution and protein levels of five chondroitin sulfate proteoglycans in spinal cord scar tissue has also shown a robust increase in two of them, NG2 and neurocan, suggesting that particularly these proteoglycans play a role in preventing axon regeneration.
44 Neurocan is synthesized and released during development, predominantly by neurons.
30 61 However, the site of neurocan synthesis switches to reactive glia after injury or degeneration, leading to an upregulation around the glial cells, as shown in adult brain, spinal cord, and retina.
19 20 37 38 42 43 44 62 63 Further, it has been shown that the upregulated neurocan is expressed in a sharp border defining the region of neuronal sprouting.
42 CD44 is normally synthesized by glial cells in the CNS and is upregulated under pathologic conditions on the surface of reactive glial cells in the brain
41 and in the retina.
34 35 39 Both CD44 and neurocan bind hyaluronan, which has been detected in the mouse IPM (Rayborn ME, et al.
IOVS 2002;43:ARVO E-Abstract 2862). CD44 has also been shown to bind to molecules modified with chondroitin sulfate proteoglycans,
64 found in the IPM as well.
37 65 66 67 Further, there is strong evidence that both CD44 and neurocan can inhibit retinal axon and neurite outgrowth.
31 32 33 It is thus reasonable to assume that these molecules could be associated with nonpermissive, reactive gliosis at the retinal outer surface and that they could contribute to limitation of the integration between abutting retinas in fragment–laminar pairs and in transplantation of fragmented tissue.