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James Edwards Morgan; Dendrite remodelling and repair in a retinal explant model of retinal ganglion cell degeneration. Invest. Ophthalmol. Vis. Sci. 2016;57(12):No Pagination Specified.
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Presentation Description :
Dendritic degeneration is a signature event in a range of degenerative diseases affecting the retina that include diabetes, glaucoma, and mitochondrial dysfunction. Retinal ganglion cells (RGCs) are ideal for the studying the events that drive this process and for exploring therapeutic interventions for dendritic repair. I will describe our use of a retinal explant model to study RGC dendritic degeneration in the mouse in which RGC degeneration is driven by axotomy. We quantify dendritic integrity using Sholl analysis applied to dendrites labelled by the particulate transfer of carbocyanine dyes (diolistics).RGCs demonstrate dendritic degeneration within 6 hours ex vivo but in the absence of significant cell death, which is not observed until day 14 . By contrast, significant reductions in Sholl area under the curve (AUC; 14.5%, p < 0.05) and branching index (41.9%, p < 0.005) are detectable at 6 hours and 1 day, respectively following RGC axotomy. The Sholl AUC was singificantly increased relative to controls following BDNF treatment initiated immediately after axotomy (75.8%, p < 0.005).Modification of the perineuronal net by digestion with chABC resulted in modest preservation of the dendritic tree but considerably less than that seen with BDNF. The combined administration of chABC and BDNF was not beneficial suggesting that glycosaminoglycan digestion exposes carbohydrate stubs, which inhibit the effect of BDNF. An important finding with this model is that the administration of BDNF after 3 days ex vivo resulted in a significant increase in RGC dendritic complexity when viewed at 6 days (136%, p < 0.001).Our data support the use of the retinal explant model to study dendritic atrophy in retinal ganglion cells in its own right but also as a sensitive readout of RGC degeneration. Since a single retina can supply several segments for running simultaneous independent experiments, retinal explants can support the rapid evaluation of novel therapeutic interventions.Funding: BBSRC (UK).
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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