Photopic flicker optoretinography captures the light-driven length modulation of photoreceptors during phototransduction

In this study, we used an inhibitor of phosphodiesterase 6 (PDE6) to
examine the impact of changes in the conformation of the PDE6 protein on
the light-induced process responsible for altering the length of the outer
segments of photoreceptor cells in both human and rodent eyes. We employed
a imaging method called spatiotemporal optical coherence tomography, which
ensures high contrast and phase stability within the strongly scattering
photoreceptor– Retinal Pigment Epithelium complex. Using this approach, we
recorded nanometer-scale changes in human cones and rods in response to
photopic flicker stimulation and observed length changes in rodent rods
under scotopic conditions following a single pulse of light, in the
absence or presence of sildenafil, which inhibits the catalytic activity
of PDE6. Our findings are consistent with the interpretation that during
phototransduction conformational changes in PDE6 structure, which occur on
an angstrom scale, are amplified to the nanometer scale due to the unique
structure of the photoreceptor outer segments and sequential stimulation.
This finding opens up possibilities for the informed use of photopic
flicker optoretinography measurements as a diagnostic tool, as the
observed nanometer-scale changes in rod and cone dimensions as a function
of light stimulus can now be directly linked to molecular events involved
in the phototransduction pathway.