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James D Lindsey; Strategies for protection of retinal ganglion cell dendrites following axonal injury. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
Presentation Description :
We have developed the capability to image the structure of RGC dendrites in vivo within a transgenic mouse strain expressing yellow fluorescent protein (YFP) under control of the promoter for Thy-1 using a modified confocal scanning laser ophthalmoscope (mCSLO). This approach allows the same RGC to be imaged repeatedly during the course of degeneration. Analysis of the shape of the dendritic trees in this model distinguished six different RGC groups. These groups correspond to nearly all of the RGC types identified in prior 3-dimensional reconstructive histological analyses. Direct overlap of the dendrite pattern revealed by YFP and a dendrite cytoskeletal protein suggests the fluorescence image corresponds to the full extent of the dendritic arbor. There are two key strengths of this approach. First, each RGC can be assigned to a particular RGC group before experimental injury alters dendrite structure. Second, subsequent changes in dendrite structure can be followed longitudinally. Using this approach, we have shown that the kinetics of dendrite degeneration following optic nerve crush differs among the RGC groups. In addition, protection against this loss of RGC dendrites by neuroprotective treatments differs among the various RGC groups. Thus, for a particular treatment, such as brimonidine, some RGC groups are protected while other groups are not. Interestingly, this pattern of protecting certain RGC groups and not others differs among RGC neuroprotective treatments that operate via different mechanisms. In conclusion, this new approach has shown that several well-known neuroprotective treatments each only protect only a portion of the total RGC population. This raises the possibility that increased potency for neuroprotective treatments to preserve or induce recovery of vision in patients with optic neuropathies such as traumatic optic neuropathy or glaucoma may be achieved by designing multi-target therapies that simultaneously provide for the various neuroprotective requirements of different RGC subtypes.
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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