Imaging outer segment renewal in living human cone photoreceptors

In vertebrate eyes, vision begins when the photoreceptor's outer segment absorbs photons and generates a neural signal destined for the brain. The extreme optical and metabolic demands of this process of phototransduction necessitate continual renewal of the outer segment. Outer segment renewal has been long studied in post-mortem rods using autoradiography, but has been observed neither in living photoreceptors nor directly in cones. Using adaptive optics, which permits the resolution of cones, and temporally coherent illumination, which transforms the outer segment into a "biological interferometer," we observed cone renewal in three subjects, manifesting as elongation of the cone outer segment, with rates ranging from 93 to 113 nm/hour (2.2 to 2.7 microm/day). In one subject we observed renewal occurring over 24 hours, with small but significant changes in renewal rate over the day. We determined that this novel method is sensitive to changes in outer segment length of 139 nm, more than 20 times better than the axial resolution of ultra-high resolution optical coherence tomography, the best existing method for depth imaging of the living retina.