Photoreceptor disc shedding in the living human eye

Abstract

Cone photoreceptors undergo a daily cycle of renewal and shedding of membranous discs in their outer segments (OS), the portion responsible for light capture. These physiological processes are fundamental to maintaining photoreceptor health, and their dysfunction is associated with numerous retinal diseases. While both processes have been extensively studied in animal models and postmortem eyes, little is known about them in the living eye, in particular human. In this study, we report discovery of the optical signature associated with disc shedding using a method based on adaptive optics optical coherence tomography (AO-OCT) in conjunction with post-processing methods to track and monitor individual cone cells in 4D. The optical signature of disc shedding is characterized by an abrupt transient loss in the cone outer segment tip (COST) reflection followed by its return that is axially displaced anteriorly. Using this signature, we measured the temporal and spatial properties of shedding events in three normal subjects. Average duration of the shedding event was 8.8 ± 13.4 minutes, and average length loss of the OS was 2.1 μm (7.0% of OS length). Prevalence of cone shedding was highest in the morning (14.3%) followed by the afternoon (5.7%) and evening (4.0%), with load distributed across the imaged patch. To the best of our knowledge these are the first images of photoreceptor disc shedding in the living retina.

In vivo optophysiology reveals that G-protein activation triggers osmotic swelling and increased light scattering of rod photoreceptors

“…As noted in the Introduction, intrinsic optical signals from individual human cone photoreceptors have been measured by a number of groups (10)(11)(12)(13)(14). The advanced state of adaptive-optics OCT methodology for the human eye enables such cone-specific intrinsic optical signals to be characterized with great precision and sensitivity, and rapid advances in measurement and clinical applicability of human photoreceptor optophysiology can certainly be expected (71).…”

“…OCT has been universally adopted in clinical ophthalmology to map human retinal layer structure (2) and is widely used for angiography of the eye (3) and heart (4,5) and for in vivo biopsy of skin and other tissues (6,7). Ocular OCT has also been used in vivo to measure "intrinsic optical signals" from the photoreceptor layer of the retina (8,9), including from individual human cone photoreceptors (10)(11)(12)(13)(14). In no case, however, has the molecular mechanism underlying an intrinsic optical signal been unequivocally identified.…”

Review of adaptive optics OCT (AO-OCT): principles and applications for retinal imaging [Invited]

“…However, using AO technology this process can now be investigated in vivo [116,117]. A recent study used AO-OCT to investigate specifically the disc shedding process in more detail [118]. 3D volumes of the cone photoreceptors were recorded during a period of 90 minutes and individual cones were tracked over time.…”

Rab28 is localised to photoreceptor outer segments, regulates outer segment shedding but is not linked to retinal degeneration in zebrafish

“…As the average distance between cone OS lamellae (9-13 nm (Nilsson 1965)) is much too small to be resolved by fluorescence microscopy, these aggregations of Rab28 must be present on only a subset of lamellae within the OS. In rods and cones, a relatively consistent number of discs/lamellae are shed each time (Kocaoglu et al 2016;Campbell & Jensen 2017). The precise reason for the rab28 pattern in cones and whether this has a functional purpose are fascinating future research questions.…”