RESTORATION OF RETINAL GANGLION CELL DENDRITIC ARBORS AFTER AXONAL INJURY IN VIVO.

Abstract

PurposeDendrites are major determinants of how retinal neurons integrate and process incoming information. We showed that retinal ganglion cells (RGCs) undergo shrinkage of dendritic arbors soon after axotomy, but the molecular mechanisms that underlie injury‐induced dendritic remodeling are poorly understood. Here, we investigated the role of the mTOR (mammalian target of rapamycin) pathway in RGC dendritic structure and synaptic input after acute optic nerve lesion.MethodsAdult transgenic mice carrying the yellow fluorescent protein (YFP) gene were subjected to optic nerve axotomy. Retinal mTOR activity was manipulated by intraocular injection of siRNA against the mTOR repressor REDD2 or by intraperitoneal administration of the mTOR inhibitor rapamycin. Retinal whole‐mounts were prepared and RGC dendritic trees were 3‐D reconstructed.ResultsOptic nerve axotomy leads to marked downregulation of mTOR activity in RGCs correlating with dendritic shrinkage prior to RGC death onset. siREDD2 stimulated mTOR activity in injured RGCs leading to increased dendritic length, surface and complexity compared to control retinas. Importantly, increased mTOR activity in RGCs restored glutamatergic bipolar cell inputs onto RGC dendritic shafts.ConclusionWe report a novel role for the mTOR pathway in the restoration of RGC dendritic arbors and excitatory synaptic input after acute optic nerve lesion.