Abstract
Limited accessibility of retinal neurons to electrophysiology on a cellular scale in-vivo have restricted studies of their physiology to in-vitro preparations and animal models. Physiological changes underlying neural signaling are mediated by changes in electrical potential that alters the surface tension of the cell membrane. In addition, physiological processes cause changes in the concentration of the constituent ions that result in variations of osmotic pressure. Both these phenomena affect the neuron’s shape which can be detected using interferometric imaging, thereby enabling non-invasive label-free imaging of the physiological activity in-vivo with cellular resolution. Here, we employ high-speed phase-resolved optical coherence tomography in line-field configuration to image the biophysical phenomena associated with phototransduction in human cone photoreceptors. 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 is driven by rapid charge movement accompanying the isomerization of cone opsins, consistent with the early receptor potential in the human electroretinography and classical electrophysiology in-vitro. We demonstrate the fidelity of such all-optical recordings of the light-induced activity in the human retina across a range of spatiotemporal scales. This approach adds functional evaluation of the retina to a routine clinical examination of the retinal structure and thus holds enormous potential to serve as an effective biomarker of photoreceptor function for early disease diagnosis and for monitoring the therapeutic efficacy.