The Study Of Axonal Regeneration And Remyelination In The Adult Zebrafish After Optic Nerve Injury

Zebrafish central nervous system (CNS) possesses a strong neural regeneration ability to restore visual function completely after optic nerve injury (ONI). However, whether neurogenesis of retinal ganglion cell (RGC) contributes to functional recovery remains controversial. Our quantitative analysis of RGCs in different ONI models showed that almost all RGCs survived in optic nerve crush (ONC) model; while over90%of RGCs survived in the first2weeks with75%remaining after7weeks in optic nerve transection (ONT) model. Retrograde labeling from tectum revealed a surprising regeneration rate, with over90%and over50%of RGCs regrowing axons to tectum at the first week in ONC and ONT model respectively. In the latter one, the number of regenerative RGCs after4weeks had no significant difference from the control group. As for neurogenesis, newborn RGCs were rarely detected either by double retrograde labeling or BrdU marker. Our results have directly shown that RGC survival and axon regrowth are responsible for functional recovery after ONI in adult zebrafish.Not like neural regeneration is not happen in mammalian, remyelination is generally happen. It is widely accepted that remyelination is the recapitulation of myelination during development. Whether mature oligodendrocytes also contribute to this procedure is still ambiguity. Here, we use the model of optic nerve injury in adult zebrafish to research remyelination during functional recovery. First, optic nerve injury induced loose myelin components and inflammation cells invasion. Second, oligodendrocytes over expressed pho-ERK1/2which indicated they began to re-enter the cell cycle. Third, oligodendrocytes whose processes still remained division in an asymmetry way, and the new born cells had a strong ability of migration. Fourth, at the first week, inflammation existing in the epicenter may play a role in repelling the migration of OPCs as NG2+astrocytes existing, with the highest TNFa level at this period; in the following weeks, OPCs were recruited into the epicenter and myelin structure was recovered, which can be delayed when inflammation was elongated by ligation of the optic nerve. Lastly, the recovery of myelin index and ranvier node, combining with the restitution of fasciculate structure, contributes to the visual functional recovery.