Optogenetic Neuroregeneration

Optogenetics is a powerful technology that employs light and genetics to manipulate physiology and behavior with unprecedented precision. The high acuity of light stimulation permits fine control both in space (e.g., to target just one tissue in an animal) and in time (e.g., to interfere with a specific disease stage), whilst genetic targeting restricts manipulation to a functionally-relevant cell population (Figure 1A). These unique capabilities have laid the ground for answering previously unresolvable questions in neuroscience and for new treatment avenues. Already shortly after its inception, optogenetics was harnessed to understand neural circuit function in animal models of neurological and neurodegenerative disorders, including spinal cord injury, stroke, and Parkinson’s disease (PD). Notably, in some of these models, optically-evoked neuronal activity was sufficient to elicit a functional improvement, e.g. through the formation of new microcircuitries or release of neurotrophic factors (Ordaz et al., 2017). These initial discoveries were recently followed by targeted neuroregeneration strategies. These generally aim at either replacement of degenerated sensory functions by optogenetic actuators or s itespecific optical delivery of pro-survival signals to counter neurodegeneration (Kleinlogel et al., 2020; Ingles-Prieto et al., 2021). It is these two optogenetic neuroregeneration strategies that we discuss here, from the origins of the field of optogenetics to the recent pioneering clinical application (Sahel et al., 2021).