Journal
JOURNAL OF NEUROSCIENCE
Volume 39, Issue 12, Pages 2313-2325Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0872-18.2018
Keywords
neuroprotection; optogenetics; retina; retinal ganglion cell; superior colliculus
Categories
Funding
- Hercules Foundation [AKUL-09-038, AKUL1309]
- Research Foundation Flanders
- Flemish government agency for Innovation by Science and Technology [110068 OPTOBRAIN, 130065 MIRIAD, S006617N Neuro-TRAFFIC]
- Funds for Research in Ophthalmology
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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.
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