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Microbial opsins for mammalian vision: Optogenetics in the retina (OptogenRet)
Date du début: 1 déc. 2012, Date de fin: 30 nov. 2017 PROJET  TERMINÉ 

The retina – a thin sheet of neural tissue in the back of the eye – is a sophisticated image processor which analyzes the incoming light pattern through a set of separate spatio-temporal channels and relays this information to the brain. The loss of the visual sense due to retinal degenerative diseases is considered to be a severe handicap for human life quality. The insertion of microbial opsins into retinal neurons is a promising approach to restore vision in retinal degenerative diseases. However, the light intensity that is needed for optogenetic stimulation is still very high, and current strategies do not allow for discrimination of different wavelengths (colour vision). To overcome these obstacles we will develop optimized optogenetic treatment strategies in mouse models of retinal degeneration by using different microbial opsins with enhanced light sensitivity and altered action spectra. Finally, by introducing microbial opsins into post mortem human retinas we will translate these optogenetic approaches into therapeutic strategies for patients who are affected by retinal degeneration.Another aim of this proposal is to investigate the structure and function of retinal interneurons that mediate the remarkable image processing capabilities of the retina. Amacrine cells represent an extremely diverse class of interneurons that contribute to visual information processing in the inner retina. Yet the function of only very few amacrine cell types is well understood. Recently, a new amacrine cell type has been identified that expresses a marker of excitatory neurons (vesicular glutamate transporter type 3, vGluT3) as well as a marker of inhibitory neurons (glycine), suggesting that this amacrine cell is a ‘dual transmitter’ neuron. However, the synaptic output of this amacrine cell remains elusive. By using optogenetics in combination with two-photon microscopy and electrophysiology we aim to uncover the function of this amacrine cell type in visual processing.