title: Retinal glia promote dorsal root ganglion axon regeneration.
abstract: Axon regeneration in the adult central nervous system (CNS) is limited by several factors including a lack of neurotrophic support. Recent studies have shown that glia from the adult rat CNS, specifically retinal astrocytes and Müller glia, can promote regeneration of retinal ganglion cell axons. In the present study we investigated whether retinal glia also exert a growth promoting effect outside the visual system. We found that retinal glial conditioned medium significantly enhanced neurite growth and branching of adult rat dorsal root ganglion neurons (DRG) in culture. Furthermore, transplantation of retinal glia significantly enhanced regeneration of DRG axons past the dorsal root entry zone after root crush in adult rats. To identify the factors that mediate the growth promoting effects of retinal glia, mass spectrometric analysis of retinal glial conditioned medium was performed. Apolipoprotein E and secreted protein acidic and rich in cysteine (SPARC) were found to be present in high abundance, a finding further confirmed by western blotting. Inhibition of Apolipoprotein E and SPARC significantly reduced the neuritogenic effects of retinal glial conditioned medium on DRG in culture, suggesting that Apolipoprotein E and SPARC are the major mediators of this regenerative response.
authors: John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, CB2 0PY, United Kingdom.
authors: Barbara
authors: B
authors: Lorber
authors: John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, CB2 0PY, United Kingdom.
authors: Daniel J
authors: DJ
authors: Chew
authors: Research Unit Protein Science, Helmholtz Center Munich, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
authors: Stefanie M
authors: SM
authors: Hauck
authors: John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, CB2 0PY, United Kingdom.
authors: Rachel S
authors: RS
authors: Chong
authors: John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, CB2 0PY, United Kingdom; Cambridge NIHR Biomedical Research Centre, Cambridge, CB2 0PY, United Kingdom.
authors: James W
authors: JW
authors: Fawcett
authors: John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, CB2 0PY, United Kingdom; Cambridge NIHR Biomedical Research Centre, Cambridge, CB2 0PY, United Kingdom; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Cambridge, United Kingdom.
authors: Keith R
authors: KR
authors: Martin
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism; D001369:Axons / Q000502:physiology*; D005727:Ganglia, Spinal / Q000166:cytology*; D008297:Male; D016501:Neurites / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism; D015676:Osteonectin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D012160:Retina / Q000166:cytology*
chemical_list: D001057:Apolipoproteins E; D015676:Osteonectin