In the retina, reactive gliosis is predominantly characterized by Müller glial activation, as indicated by upregulation of intermediate filament proteins such as glial fibrillary acidic protein (GFAP) ( Figure 3(a), red) and the projection of processes from their original location (forming the outer limiting membrane) into the subretinal space. Why then are attempts at stimulating retinal regeneration via stem cell transplantation still largely unsuccessful? The lack of functional integration following transplantation is in large part due to the presence of an inhibitory injury induced glial scar that forms during reactive gliosis. Thus, these factors are not a concern when attempting to stimulate regeneration in retinal degenerative diseases such as RP and AMD, both of which predominantly affect the retinal outer nuclear layer. Unlike the optic nerve, the retina is void of myelin, oligodendrocytes, and their associated inhibitory ECM molecules. Thus, in order for stem cell therapies to be used as an effective treatment for diseases such as glaucoma, which affect the retinal ganglion cell layer and optic nerve, inhibition of these proteins will ultimately be required. The optic nerve, like other CNS locations, is laden with these inhibitory proteins, and as such, their chemical and/or enzymatic neutralization has been shown to significantly enhance retinal ganglion cell axon extension and optic nerve regeneration. Unlike the peripheral nervous system (PNS), the central nervous system (CNS) is stricken with an abundance of myelin-associated extracellular matrix (ECM) proteins, namely MAG, Nogo, and Omgp, which are well known for their ability to inhibit process extension and functional regeneration. As suggested above, a major contributor to the lack of functional regeneration in the face of efficient cell delivery is the presence of an inhibitory extracellular environment. Klassen, in Encyclopedia of the Eye, 2010 Inhibitory BarriersĪlthough we have developed an efficient means of cell delivery, in order to achieve functional regeneration via retinal reconstruction/repopulation, a further increase in cellular integration and axonal extension/synapse formation is required.
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