Retinal glia promote dorsal root ganglion axon regeneration.

Barbara Lorber,Rachel S Chong,Keith R Martin,Stefanie M Hauck,James W Fawcett,Daniel J Chew

doi:10.1371/journal.pone.0115996

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.

Highlights

Axon regeneration in the adult central nervous system (CNS) is limited by several factors including axon growth inhibitory molecules such as chondroitin sulphate proteoglycans and growth cone collapsing myelin products along the pathway of growing axons [1], intrinsic changes in the growth capacity of maturing neurons [2] and lack of trophic support [3].Several glial cell types have previously been shown to provide neuronal trophic support
We found that retinal glial conditioned medium significantly enhanced neurite growth (P
We found that retinal glial conditioned medium strongly enhanced neurite growth and branching of adult DRG in culture, and chose the dorsal root crush model to investigate whether retinal glia stimulate regeneration in the mature CNS outside the visual system

Summary

Introduction

Several glial cell types have previously been shown to provide neuronal trophic support. These include peripheral nervous system (PNS)-derived Schwann cells, CNS-derived oligodendrocyte precursor cells, and olfactory ensheathing cells, a distinct glial cell type found in the olfactory system but sharing a common developmental heritage with Schwann cells [4], [5]. Retinal Glia and Dorsal Root Ganglion Regeneration. Retinal glia were found to stimulate retinal ganglion cell neurite growth in vitro and to be important mediators of the repair response occurring in optic nerve regeneration and glaucoma models in vivo [6,7,8]

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Results

Conclusion