The optoretinogram reveals how human photoreceptors deform in response to light

Abstract

Limited accessibility of retinal neurons to electrophysiology on a cellular scale in-vivo has restricted studies of their signaling to in-vitro preparations and animal models. Physiological changes underlying neural activity are mediated by variations in electrical potential that alter the surface tension of the cell membrane. In addition, physiological processes affect concentration of the cells constituents that results in variation of osmotic pressure. Both these phenomena affect the neurons shape which can be detected using interferometric imaging, thereby enabling non-invasive label-free imaging of physiological activity in-vivo with cellular resolution. Here, we apply high-speed phase-resolved optical coherence tomography in line-field configuration to image the biophysical phenomena associated with phototransduction in human cone photoreceptors in vivo. We demonstrate that individual cones exhibit a biphasic response to light: an early ms-scale fast contraction of the outer segment immediately after the onset of the flash stimulus followed by a gradual (hundreds of ms) expansion. We demonstrate that the contraction can be explained by rapid charge movement accompanying the isomerization of cone opsins, consistent with the early receptor potential observed in the electroretinogram and classical electrophysiology in-vitro. We demonstrate the fidelity of such all-optical recording of light-induced activity in the human retina, namely the optoretinogram, across a range of spatiotemporal scales. This approach incorporates functional evaluation into a routine clinical examination of retinal structure and thus holds enormous potential to serve as a biomarker for early disease diagnosis and monitoring therapeutic efficacy.