On mechanisms of light-induced deformations in photoreceptors

Boyle, Kevin C.; Chen, Zhijie Charles; Ling, Taotao; Pandiyan, Vimal Prabhu; Kuchenbecker, James A.; Sabesan, Ramkumar; Palanker, Daniel

doi:10.1101/2020.01.08.897728

Cited by 5 publications

(8 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Second, it matches the time course of the deformation at different stimulus intensities, specifically the earlier time to peak at higher stimulus intensity, as shown in Fig 3c (also see Fig 2f and Fig S2). The excellent agreement of the model with the experimental results, being consistent in peak deformation and timing across all stimulus intensities with a single set of model parameters ( , , , and ), indicates that the contraction of the outer segment is an optical signature of the ERP 29 .…”

Section: Energy Dependence Of the Early And Late Cone Responsesupporting

confidence: 63%

See 1 more Smart Citation

The optoretinogram reveals how human photoreceptors deform in response to light

Kuchenbecker

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Limited accessibility of retinal neurons to electrophysiology on a cellular scale in-vivo has restricted studies of their signaling to in-vitro preparations and animal models. Physiological changes underlying neural activity are mediated by variations in electrical potential that alter the surface tension of the cell membrane. In addition, physiological processes affect concentration of the cell's constituents that results in variation of osmotic pressure. Both these phenomena affect the neuron's shape which can be detected using interferometric imaging, thereby enabling non-invasive label-free imaging of physiological activity in-vivo with cellular resolution. Here, we apply high-speed phase-resolved optical coherence tomography in line-field configuration to image the biophysical phenomena associated with phototransduction in human cone photoreceptors in vivo. We demonstrate that individual cones exhibit a biphasic response to light: an early ms-scale fast contraction of the outer segment immediately after the onset of the flash stimulus followed by a gradual (hundreds of ms) expansion. We demonstrate that the contraction can be explained by rapid charge movement accompanying the isomerization of cone opsins, consistent with the early receptor potential observed in the electroretinogram and classical electrophysiology in-vitro. We demonstrate the fidelity of such all-optical recording of light-induced activity in the human retina, namely the optoretinogram, across a range of spatiotemporal scales. This approach incorporates functional evaluation into a routine clinical examination of retinal structure and thus holds enormous potential to serve as a biomarker for early disease diagnosis and monitoring therapeutic efficacy.

show abstract

Section: Energy Dependence Of the Early And Late Cone Responsesupporting

confidence: 63%

“…Here we outline the key components of the model. A more detailed elaboration of the model appears in a companion article 29 . The membrane area expansion coefficient increases with tension as a result of flattening the thermally induced fluctuations 30 .…”

Section: Energy Dependence Of the Early And Late Cone Responsementioning

confidence: 99%

The optoretinogram reveals how human photoreceptors deform in response to light

Kuchenbecker

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…The late response has been attributed to be the influx of water to maintain osmotic balance during the phototransduction cascade 15 . Based on the latency and the magnitude of the stimulus strength that characterize the rapid shrinkage, we earlier concluded that the reduction in OPL is the optical manifestation of the early receptor potential observed previously in vitro, attributed to charge movement across the outer segment disc membranes during photoisomerization 39,[45][46][47] . Similar experiments as Figure 5 were repeated with the increased resolution offered by AO that allowed discerning the ORG in individual cones, in response to the 660 nm stimulus.…”

Section: Figure 5: Optoretinograms With 660 Nm Stimulus Acquired Withmentioning

confidence: 89%

“…The key featureshigh speed, anamorphic detection, AO or non-AO operationsummarized above are fundamental to the application of this novel technology for interferometric imaging of neural activity in photoreceptors and holds promise for future applications to other retinal cells in general. While this work represents an important step forward in the technology for all-optical, non-invasive interrogation of retinal activity, understanding the underlying mechanisms 15, 39,45 of such optoretinograms is key for its application as a biomarker to study basic visual processes and retinal health in disease and therapies.…”

Section: Discussionmentioning

confidence: 99%

High-speed adaptive optics line-scan OCT for cellular-resolution optoretinography

Pandiyan

Jiang

Bertelli

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Optoretinographythe non-invasive, optical imaging of light-induced functional activity in the retinastands to provide a critical biomarker for testing the safety and efficacy of new therapies as well as their rapid translation to the clinic. Optical phase change in response to light, as readily accessible in phaseresolved OCT, offers a path towards all-optical imaging of retinal function. However, typical human eye motion adversely affects phase stability and precludes the recording of fast light-induced retinal events.Here we introduce a high-speed line-scan spectral domain OCT with adaptive optics (AO), aimed at volumetric imaging and phase-resolved acquisition of retinal responses to light. By virtue of parallel acquisition of an entire retinal cross-section (B-scan) in a single high-speed camera frame, depth-resolved tomograms at speeds up to 16 kHz were achieved with high sensitivity and phase stability. To optimize spectral and spatial resolution, an anamorphic detection paradigm was introduced enabling improved light collection efficiency and signal roll-off compared to traditional methods. The benefits in speed, resolution and sensitivity were exemplified in imaging nanometer-millisecond scale light-induced optical path length changes in cone photoreceptor outer segments. With 660 nm stimuli, individual cone responses readily segregated into three clusters, corresponding to long, middle and short-wavelength cones. Recording such optoretinograms on spatial scales ranging from individual cones, to 100 µm-wide retinal patches offers a robust and sensitive biomarker for cone function in health and disease. Furthermore, incorporating this capability into an easy-to-use and ubiquitous diagnostic platform of OCT enables its widespread application to patient care and drug development.

show abstract

“…The agreement of the model with the experimental results, being consistent in peak deformation and timing across all stimulus strengths with a single set of model parameters (m, c, k, and l), indicates that contraction of the outer segment is indeed driven by the charge transfer across the membrane during ERP. A more detailed description of the model linking the underlying biophysical properties of the membrane to these phenomenological parameters is described elsewhere (33).…”

Section: Mechanism Of Cone Outer Segment Contractionmentioning

confidence: 99%

The optoretinogram reveals the primary steps of phototransduction in the living human eye

et al. 2020

Self Cite

View full text Add to dashboard Cite

Photoreceptors initiate vision by converting photons to electrical activity. The onset of the phototransduction cascade is marked by the isomerization of photopigments upon light capture. We revealed that the onset of phototransduction is accompanied by a rapid (<5 ms), nanometer-scale electromechanical deformation in individual human cone photoreceptors. Characterizing this biophysical phenomenon associated with phototransduction in vivo was enabled by high-speed phase-resolved optical coherence tomography in a line-field configuration that allowed sufficient spatiotemporal resolution to visualize the nanometer/millisecond-scale light-induced shape change in photoreceptors. The deformation was explained as the optical manifestation of electrical activity, caused due to rapid charge displacement following isomerization, resulting in changes of electrical potential and surface tension within the photoreceptor disc membranes. These all-optical recordings of light-induced activity in the human retina constitute an optoretinogram and hold remarkable potential to reveal the biophysical correlates of neural activity in health and disease.

show abstract

On mechanisms of light-induced deformations in photoreceptors

Cited by 5 publications

References 25 publications

The optoretinogram reveals how human photoreceptors deform in response to light

The optoretinogram reveals how human photoreceptors deform in response to light

High-speed adaptive optics line-scan OCT for cellular-resolution optoretinography

The optoretinogram reveals the primary steps of phototransduction in the living human eye

Contact Info

Product

Resources

About