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An Beckers, Ilse Bollaerts, Jessie Van houcke, Kim Lemmens, Lieve K M Moons; A temporal correlation between axonal regeneration and dendrite remodeling in adult zebrafish?. Invest. Ophthalmol. Vis. Sci. 2016;57(12):749.
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© ARVO (1962-2015); The Authors (2016-present)
Besides axonal degeneration and retinal ganglion cell (RGC) death, optic neuropathies are characterized by retinal synaptic losses and RGC dendritic shrinkage. As neuroprotective strategies are insufficient to reestablish dendrite morphology, maintenance/restoration of dendritic arbors gains ground as an important therapeutic approach in regenerative research. Zebrafish possess unique regenerative capacities and are considered ideal model organisms to identify mechanisms underlying CNS repair. We applied the optic nerve crush (ONC) model to map synaptic and dendrite responses of inner retinal neurons during axonal regeneration in adult zebrafish.
To define axonal regeneration, the retinal GAP-43 expression pattern was determined via western blotting (WB) and immunohistochemistry. Biocytin labeling was used to map optic tectum reinnervation. Dendritic remodeling was studied via morphometric analysis of inner plexiform layer (IPL) thickness on H&E stained retinal sections and by protein quantification of dendrite (MAP2) and synapse (SV2) markers via WB.
In naive fish, GAP-43 was expressed in RGC dendrites, suggestive of a continuous synaptic shifting or dendritic growth. At 4 days post injury (dpi), GAP-43 was highly upregulated in RGC somata and axons, but decreased in the IPL, respectively indicating axonal regeneration and dendrite retraction. The latter was further supported by a significant decrease in IPL thickness and MAP2 and SV2 expression at 4 dpi. Optic tectum reinnervation was fully ongoing at 7dpi and appeared completed at 14dpi, as confirmed by axonal GAP-43 expression that re-approached control levels. Notably, from 7-14dpi, GAP-43 signal reappeared in IPL dendrites and IPL thickness was restored. Furthermore, MAP2 and SV2 expression was fully recovered at 14dpi, suggestive of dendritic repair during tectal reinnervation.
Similar to mammals, optic nerve injury induces synaptic degeneration and dendrite shrinkage in the retina of zebrafish. This dendrite retraction occurs during the RGC axonal regrowth phase. Furthermore, upon RGC target reinnervation, RGC dendrites of zebrafish appear able to regain their morphology and synaptic connectivity. These data suggest that injured RGCs in adult zebrafish recapitulate development, where RGCs first show an axonal growth mode, followed by dendrite maturation.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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