Optogenetic Stimulation of the Superior Colliculus Confers Retinal Neuroprotection in a Mouse Glaucoma Model
| Autor: | Chris Van den Haute, Emiel Geeraerts, Eline Dekeyster, Lieve Moons, Veerle Baekelandt, Isabelle Scheyltjens, Lies De Groef, Manuel Salinas-Navarro, Marie Claes, Lutgarde Arckens |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Retinal Ganglion Cells Superior Colliculi genetic structures Glaucoma Stimulation Optogenetics Retinal ganglion Neuroprotection 03 medical and health sciences 0302 clinical medicine medicine Animals Research Articles Neurons Retina business.industry General Neuroscience Superior colliculus medicine.disease eye diseases Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure Retinal ganglion cell Female sense organs business Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 39(12) |
| ISSN: | 1529-2401 |
| Popis: | Glaucoma 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.SIGNIFICANCE STATEMENT Despite glaucoma being a leading cause of blindness and visual impairment worldwide, no curative therapies exist. This study describes a novel paradigm to reduce retinal ganglion cell (RGC) degeneration underlying glaucoma. Building on previous observations that RGC survival is supported by the target neurons to which they project and using an innovative optogenetic approach, we increased neuronal activity in the mouse superior colliculus, a main projection target of rodent RGCs. This proved to be efficient in reducing RGC loss in a glaucoma model. Our findings establish a new optogenetic paradigm for target stimulation and encourage further exploration of the molecular signaling pathways mediating retrograde neuroprotective communication. ispartof: Journal Of Neuroscience vol:39 issue:12 pages:2313-2325 ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
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