Browsing by Subject "Optogenetics"
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- PublicationOpen AccessB12-based photoreceptors: from structure and function to applications in optogenetics and synthetic biology(2019-08) Pérez-Castaño, Ricardo; Elías Arnanz, Montserrat; Padmanabhan Iyer, Subramanian; Genética y MicrobiologíaVitamin B12-based photoreceptor proteins sense ultraviolet (UV), blue or green light using 5´-deoxyadenosylcobalamin (AdoCbl). The prototype of this widespread bacterial photoreceptor family, CarH, controls light-dependent gene expression in photoprotective cellular responses. It represses transcription in the dark by binding to operator DNA as an AdoCbl-bound tetramer, whose disruption by light relieves operator binding to allow transcription. Structures of the "dark" (free and DNA-bound) and "light" CarH states and studies on the unusual AdoCbl photochemistry have provided fundamental insights into these photoreceptors. We highlight these, the plasticity within a conserved mode of action among CarH homologs, their distribution, and their promising applications in optogenetics and synthetic biology.
- PublicationOpen AccessOptogenetic Stimulation of the Superior Colliculus Confers Retinal Neuroprotection in a Mouse Glaucoma Model(Society for Neuroscience, 2019-03-20) Geeraerts, Emiel ; Claes, Marie ; Dekeyster, Eline; Salinas Navarro, Manuel Ángel; De Groef, Lies ; Van den Haute, Chris ; Scheyltjens, Isabelle ; Baekelandt, Veerle ; Arckens, Lutgarde ; Moons, Lieve ; Anatomía Humana y Psicobiología; Facultades de la UMU::Facultad de MedicinaGlaucoma is characterized by a progressive loss of retinal ganglion cells (RGCs) in the eye, which ultimately results in visual impairment or even blindness. Because current therapies often fail to halt disease progression, there is an unmet need for novel neuroprotective therapies to support RGC survival. Various research lines suggest that visual target centers in the brain support RGC functioning and survival. Here, we explored whether increasing neuronal activity in one of these projection areas could improve survival of RGCs in a mouse glaucoma model. Prolonged activation of an important murine RGC target area, the superior colliculus (SC), was established via a novel optogenetic stimulation paradigm. By leveraging the unique channel kinetics of the stabilized step function opsin (SSFO), protracted stimulation of the SC was achieved with only a brief light pulse. SSFO-mediated collicular stimulation was confirmed by immunohistochemistry for the immediate-early gene c-Fos and behavioral tracking, which both demonstrated consistent neuronal activity upon repeated stimulation. Finally, the neuroprotective potential of optogenetic collicular stimulation was investigated in mice of either sex subjected to a glaucoma model and a 63% reduction in RGC loss was found. This work describes a new paradigm for optogenetic collicular stimulation and a first demonstration that increasing target neuron activity can increase survival of the projecting neurons.