Endogenous Redox-Photonic Signaling in Mammalian Neurons

Objective

Vision is enabled by photoreceptor proteins in the eye called opsins. In addition to visual opsins, mammals also possess three non-visual opsins, which are highly conserved and also expressed in extra-ocular tissues such as the brain. Recent studies in live mice have shown that these non-canonical opsins are both light-responsive and physiologically active. However, the poor penetration of visible light through hair, skin, bone, and tissue, raises intriguing questions about whether environmental light can conceivably activate opsins found in regions as dark as the inner brain of nocturnal mammals. I hypothesized that these deep-tissue opsins may be activated by an alternative, internal, source. Specifically, reactive oxygen and nitrogen species (ROS/RNS) can react with cellular biomolecules to form excited states capable of light emission. This chemiluminescence phenomenon was studied intensively decades ago, but has since been overlooked. In the past years, I have established a multi-disciplinary research group aimed at tackling this hypothesis and we have obtained substantial evidence that redox-induced reactions are indeed capable of activating the non-visual opsin 3 (OPN3) in mouse hippocampal neurons in a process that we term “redox-photonic signaling”. However, many fundamental questions remain. In PhotonSignaling, we will 1) Determine the precise mechanisms of redox-photonic signaling, 2) Determine the physiological consequences of this signaling pathway in mouse neurons, and 3) Explore the extension of this pathway to a broader signaling paradigm. PhotonSignaling introduces a new dimension to redox biology, photosensory proteins, and cellular signaling. Through this lens, our work has the potential to reshape our understanding of fundamental biology, such as the role of neuropeptides and neurotransmitters, of physiological processes such as aging, and of diseases such as neurodegeneration, to ultimately unlock conceptually new therapeutic interventions.