Functional intrinsic optical signal imaging for objective optoretinography of human photoreceptors

Functional mapping of photoreceptor physiology is important for better disease diagnosis and treatment assessment. Fast intrinsic optical signal (IOS), which arises before light-evoked pupillary response, promises a unique biomarker of photoreceptor physiology for objective optoretinography with high resolution. This study is to test the feasibility of non-mydriatic IOS mapping of retinal photoreceptors in awake human. Depth-resolved optical coherence tomography verified outer segment (OS) as the anatomic origin of fast photoreceptor-IOS. Dynamic IOS changes are primarily confined at OS boundaries connected with inner segment and retinal pigment epithelium, supporting transient OS shrinkage due to phototransduction process as the mechanism of the fast photoreceptor-IOS response.

Fast intrinsic optical signal correlates with activation phase of phototransduction in retinal photoreceptors

Quantitative assessment of physiological condition of retinal photoreceptors is desirable for better detection and treatment evaluation of eye diseases that can cause photoreceptor dysfunctions. Functional intrinsic optical signal (IOS) imaging, also termed as optoretinography (ORG) or optophysiology, has been proposed as a high-resolution method for objective assessment of retinal physiology. Fast IOS in retinal photoreceptors shows a time course earlier than that of electroretinography a-wave, promising an objective marker for noninvasive ORG of early phototransduction process in retinal photoreceptors. In this article, recent observations of fast photoreceptor-IOS in animal and human retinas are summarized, and the correlation of fast photoreceptor-IOS to five steps of phototransduction process is discussed. Transient outer segment conformational change, due to inter-disc space shrinkage correlated with activation phase of phototransduction, has been disclosed as a primary source of the fast photoreceptor-IOS. Impact statement As the center of phototransduction, retinal photoreceptors are responsible for capturing and converting photon energy to bioelectric signals for following visual information processing in the retina. This article summarizes experimental observation and discusses biophysical mechanism of fast photoreceptor-intrinsic optical signal (IOS) correlated with early phase of phototransduction. Quantitative imaging of fast photoreceptor-IOS may provide objective optoretinography to advance the study and diagnosis of age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy, and other eye diseases that can cause photoreceptor dysfunctions.

Comparative study of wild-type and rd10 mice reveals transient intrinsic optical signal response before phosphodiesterase activation in retinal photoreceptors

Transient intrinsic optical signal (IOS) has been observed in stimulus-evoked retinal photoreceptors. This study is to compare IOS changes in wild-type and retinal degeneration 10 (rd10) mouse retinas, to evaluate the effect of cyclic guanosine monophosphate phosphodiesterase on photoreceptor-IOS. Time-lapse near-infrared light microscopy was employed to monitor the spatiotemporal dynamics of the IOS responses in freshly isolated retinas activated by visible light stimulation. Comparative IOS recordings were conducted at postnatal days 14 (P14) and P16. At P14, intrinsic optical signal magnitudes and spatiotemporal dynamics in wild-type and rd10 retinas were similar, indicating that the phosphodiesterase deficiency in rd10 did not affect the formation of photoreceptor-IOS. At P16, IOS magnitude in rd10 significantly decreased compared to that in wild-type, suggesting the IOS sensitivity to the photoreceptor degeneration in rd10. Our experimental results and theoretical analysis indicate that early disc-based stages of the phototransduction cascade before the activation of phosphodiesterase may contribute to the formation of the photoreceptor-IOS responses; and the IOS can be a sensitive biomarker for objective assessment of retinal function. Impact statement Comparative study of wild-type and rd10 mice was implemented to reveal that transient intrinsic optical signal (IOS) was initiated before the phosphodiesterase activation in stimulus-activated photoreceptors and the IOS magnitude was sensitive to photoreceptor degeneration. The photoreceptor-IOS promises a noninvasive biomarker for objective assessment of age-related macular degeneration, retinitis pigmentosa, and other eye diseases that can produce photoreceptor dysfunctions.