Abstract
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 over 90% of RGCs survived in the first 2 weeks with 75% remaining after 7 weeks in optic nerve transection (ONT) model. Retrograde labeling from tectum revealed a surprising regeneration rate, with over 90% and over 50% 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 after 4 weeks had no significant difference from the control group. As for neurogenesis, newborn RGCs were rarely detected either by double retrograde labeling or BrdU marker. Since few RGCs died, microglia number showed a temporary increase at 3 days post injury (dpi) and a decrease at 14 dpi. Finally, myelin structure within retina kept integrity and optomotor response (OMR) test demonstrated visual functional restoration at 5 weeks post injury (wpi). In conclusion, our results have directly shown that RGC survival and axon regrowth are responsible for functional recovery after ONI in adult zebrafish.
Highlights
Optic nerve injury often induces massive cell death and irreversible visual functional impairment in mammals, such as mouse 1], rat 2,3], rabbit 4], and cat 5]
All these results indicate a strong ability of zebrafish retinal ganglion cell (RGC) to survive after optic nerve injury (ONI)
RGCs died after ONI in rat retina, we considered that perhaps the inflammatory responses in zebrafish might affect RGCs survived after ONI 41]
Summary
Optic nerve injury often induces massive cell death and irreversible visual functional impairment in mammals, such as mouse 1], rat 2,3], rabbit 4], and cat 5]. Like quail 6], Rana pipiens 7] and Litoria moorei 8], can recover visual function due to retinal ganglion cell (RGC) survival. About 90% of RGCs survive and rapidly regrow axons to tectum about 2 weeks after axotomy 9]. Being a member of lower vertebrates and a model organism, zebrafish has excellent potential to regenerate RGC axon to tectum within 5 days after optic nerve crush (ONC) 10]. It can restore visual function at 20– 25 dpi 11], comparing with 40 days for cichlid 12], 30–50 days for goldfish 13] and 16 weeks for sunfish 14]. Whether RGC survival or neurogenesis is required for visual functional recovery is still a matter of controversy 15]
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