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
نویسندگان
چکیده
EXPRESSION OF MICROBIAL RHODOPSINS IN RETINALNEURONS WITH SUBCELLULAR TARGETING MOTIFS: FOR THESTUDY OF THE STRUCTURE/FUNCTION OF AII AMACRINECELLS AND FOR VISION RESTORATIONbyCHAOWEN WUAugust 2011Advisor: Dr. Zhuo-Hua PanMajor: Anatomy & Cell BiologyDegree: Doctor of Philosophy Protein-targeting motifs serve as addresses for subcellularprotein localization. This feature of targeting-motifs was used to studythe retina. The first part of the dissertation reports in the axonlessspiking AII amacrine cell of the mammalian retina a dendritic processsharing organizational and functional similarities with the axon initialsegment, the typical site of action potential initiation. This process wasrevealed 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 ofthe dissertation aimed to improve microbial rhodopsin-mediated genetherapy for vision restoration by using targeting-motifs to recreate87
منابع مشابه
rAAV-Mediated Subcellular Targeting of Optogenetic Tools in Retinal Ganglion Cells In Vivo
Expression of optogenetic tools in surviving inner retinal neurons to impart retinal light sensitivity has been a new strategy for restoring vision after photoreceptor degeneration. One potential approach for restoring retinal light sensitivity after photoreceptor degeneration is to express optogenetic tools in retinal ganglion cells (RGCs). For this approach, restoration of ON and OFF center-s...
متن کاملEctopic expression of multiple microbial rhodopsins restores ON and OFF light responses in retinas with photoreceptor degeneration.
By expressing channel rhodopsin-2 (ChR2) in inner retinal neurons, previous studies have demonstrated restoration of ON responses in the retina after the death of rod and cone photoreceptors. In this study, we report that the expression of halorhodopsin (HaloR), a light-driven chloride pump, can effectively restore OFF responses in inner retinal neurons of mice with retinal degeneration. We sho...
متن کاملThe AII amacrine cell connectome: a dense network hub
The mammalian AII retinal amacrine cell is a narrow-field, multistratified glycinergic neuron best known for its role in collecting scotopic signals from rod bipolar cells and distributing them to ON and OFF cone pathways in a crossover network via a combination of inhibitory synapses and heterocellular AII::ON cone bipolar cell gap junctions. Long considered a simple cell, a full connectomics ...
متن کاملAction potential generation at an axon initial segment-like process in the axonless retinal AII amacrine cell.
In axon-bearing neurons, action potentials conventionally initiate at the axon initial segment (AIS) and are important for neuron excitability and cell-to-cell communication. However in axonless neurons, spike origin has remained unclear. Here we report in the axonless, spiking AII amacrine cell of the mouse retina a dendritic process sharing organizational and functional similarities with the ...
متن کاملEvaluation of the adeno-associated virus mediated long-term expression of channelrhodopsin-2 in the mouse retina
PURPOSE The conversion of inner retinal neurons to photosensitive cells via viral mediated expression of channelrhodopsin-2 (ChR2) offers a new potential approach for the restoration of vision after photoreceptor degeneration. This study was conducted to evaluate the recombinant adeno-associated virus serotype 2 (rAAV2)-mediated long-term expression and safety of ChR2 in the mouse retina. MET...
متن کامل