Abstract
Presentation Description :
Photoreceptors initiate vision by converting photons to electrical activity via the process of phototransduction. Recent developments in high-resolution imaging have allowed biophysical correlates of cone phototransduction to be measured in a living human eye. Specifically, our lab has used high-speed, phase-resolved optical coherence tomography that provides sufficient spatiotemporal resolution to visualize nanometer/millisecond-scale, light-driven length changes in individual cone outer segments (COS), measurements now generally called the optoretinogram (ORG). The ORG affords a non-invasive, label-free, functional assay of cone viability. We have found three distinct components of the cone ORG, each with a characteristic amplitude, photosensitivity (bleach-level dependence) and kinetics. Responses comprised a fast phase (∼5 ms), during which COS shrink, and two slower phases (time constants of rise: 80 ms and 1s), during which COS elongate. As photoisomerization initiates the ORG, the quantification of cone pigment bleaching in living human eyes is critical to establishing its mechanistic basis. Response families to stimuli bleaching up to 99% of L- and M-cone opsins allowed testing and constraining hypotheses for the molecular mechanisms of human COS elongation. In this talk, I will briefly describe the technologies that enable the ORG recordings and pigment bleaching in vivo in humans. Next, I will describe critical discrepancies amongst extant measures of cone pigment bleaching, and our efforts to resolve this problem. I will conclude with a summary of the molecular mechanisms currently hypothesized to underlie each component of the cone ORG, relating the components with specific events during phototransduction. Together, these studies provide a basis for the assessment of phototransduction in human cones with ORG in health, and during disease progression and therapeutic interventions.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.