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Date of Award
Anatomy and Cell Biology
Protein-targeting motifs serve as addresses for subcellular protein localization. This feature of targeting-motifs was used to study the retina. The first part of the dissertation reports in the axonless spiking AII amacrine cell of the mammalian retina a dendritic process sharing organizational and functional similarities with the axon initial segment, the typical site of action potential initiation. This process was revealed through viral-mediated expression of channelrhodopsin-2-GFP (ChR2-GFP) with the AIS-targeting motif of sodium channels (NavII-III) and was shown to be the site of spike initiation. The second part of the dissertation aimed to improve microbial rhodopsin-mediated gene therapy for vision restoration by using targeting-motifs to recreate center-surround antagonism in retinal ganglion cells (RGCs). Results of the study showed that a smaller center and a larger encompassing surround receptive field can be generated directly in a single RGC both morphologically and physiologically through the use of protein targeting motifs. Motif-targeting may be a promising approach in restoring center-surround antagonism in the RGC despite bypassing intraretinal processing.
Wu, Chaowen, "Expression of microbial rhodopsins in retinal neurons with subcellular targeting motifs: for the study of the structure/function of aii amacrine cells and for vision restoration" (2011). Wayne State University Dissertations. Paper 362.