Retinal ganglion cell axons regrow despite persistent astrogliosis in the lizard

Romero-Alemán, M. d. M. 1 , Monzón-Mayor, M. 1 , Santos, E. 2 & Yanes, C. M. 2

1 Universidad de Las Palmas de Gran Canaria
2 Universidad de La Laguna

We analysed the astroglia response that is concurrent with spontaneous axonal regrowth after optic nerve (ON) transection in the lizard Gallotia galloti. At different post-lesional time points (0.5 to 12 months), we used conventional electron microscopy and specific markers for astrocytes (GFAP, vimentin (Vim), Sox9, Pax2) and for proliferating cells (PCNA). In the experimental retina the increase of gliofilaments was not significant and proliferating cells were undetectable. Conversely, PCNA+/GFAP+ and PCNA+/Vim+ reactive astrocytes were identified in the regenerating ON and optic tract (OTr). They up-regulated Vim at 1 month post-lesion, and both Vim and GFAP at 12 months post-lesion, indicating long-term astrogliosis. They also expressed Pax2, Sox9 in the ON, and Sox9 in the OTr. Concomitantly, persistent tissue cavities and disorganised regrowing fibre bundles reaching the OT were observed. Our ultrastructural data confirm abundant gliofilaments in reactive astrocytes joined by desmosomes. Remarkably, they also accumulated myelin debris and lipid droplets until late stages, indicating their participation in myelin removal. These data suggest that persistent mammalian-like astrogliosis in the adult lizard ON contributes to a permissive structural scaffold for long-term axonal regeneration and provides a useful model to study the molecular mechanisms involved in these beneficial neuron-glia interactions. This work was supported by the Spanish Ministry of Education (Research Project BFU2007-67139), the Regional Canary Island Government (ACIISI, Research Projects SolSub200801000281 and ULPAPD-08/012-4).