Brighten the Future: Photobiomodulation and Optogenetics.

Safe, noninvasive, and effective treatments for brain conditions are everyone's dream. Low-level light therapy (LLLT) based on the photobiomodulation (PBM) phenomenon has recently been adopted in practice, with solid scientific evidence. Optogenetics provides high spatiotemporal resolution to precisely switch on and off a particular circuitry in the brain. However, there are currently no human trials of optogenetics on the human brain. These two approaches-PBM and optogenetics-are promising photonic treatments that target the brain using completely different technologies. PBM is based on the mitochondrial reaction to the photons for up- or downregulation on the cytochrome c oxidase synthase in cellular respiration. It is safe, noninvasive, and good for long-term treatments, with wide applications using light wavelengths ranging from 650 nm to ≈1,100 nm, the red to near-infrared range. Optogenetics is based on the expression of engineered opsins on targeted tissues through viral vectors. The opsins are engineered to be sensors, actuators, or switches and could be precisely controlled by light wavelength ranging from 450 nm to ≈650 nm, the visible light range. The penetration of visible light is limited, and thus the photons cannot be applied directly outside the head without surgical means to create a physical window. PBM using near-infrared light could reach deeper tissues for light directly applied outside the head. Detailed scientific foundations and the state of the art for both technologies are reviewed. Ongoing developments are discussed to provide insight for future research and applications.