Cone photoreceptor classification in the living human eye from photostimulation-induced phase dynamics

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 116; no. 16; pp. 7951 - 7956
• Main Authors: Zhang, Furu, Kurokawa, Kazuhiro, Lassoued, Ayoub, Crowell, James A., Miller, Donald T.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 16.04.2019
• Subjects: Adaptive optics; Adult; Biological Sciences; Blurring; Color; Color blindness; Color vision; Color Vision - physiology; Cone classifiers; Cones; Densitometers; Densitometry; Downstream effects; Dynamics; Eye; Humans; Image acquisition; Image Processing, Computer-Assisted; Information processing; Male; Middle Aged; Optical Coherence Tomography; Optics; Phase transitions; Photic Stimulation - methods; Photoactivation; Photoreception; Photoreceptors; Phototransduction; Physical Sciences; Retina; Retina - diagnostic imaging; Retina - physiology; Retinal Cone Photoreceptor Cells - classification; Retinal Cone Photoreceptor Cells - physiology; Tomography, Optical Coherence; Wavelengths; Young Adult; adaptive optics; cone classification; optical coherence tomography; retina; color vision
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1816360116

Human color vision is achieved by mixing neural signals from cone photoreceptors sensitive to different wavelengths of light. The spatial arrangement and proportion of these spectral types in the retina set fundamental limits on color perception, and abnormal or missing types are responsible for color vision loss. Imaging provides the most direct and quantitative means to study these photoreceptor properties at the cellular scale in the living human retina, but remains challenging. Current methods rely on retinal densitometry to distinguish cone types, a prohibitively slow process. Here, we show that photostimulation-induced optical phase changes occur in cone cells and carry substantial information about spectral type, enabling cones to be differentiated with unprecedented accuracy and efficiency. Moreover, these phase dynamics arise from physiological activity occurring on dramatically different timescales (from milliseconds to seconds) inside the cone outer segment, thus exposing the phototransduction cascade and subsequent downstream effects. We captured these dynamics in cones of subjectswith normal color vision and a deuteranope, and at different macular locations by: (i) marrying adaptive optics to phase-sensitive optical coherence tomography to avoid optical blurring of the eye, (ii) acquiring images at high speed that samples phase dynamics at up to 3 KHz, and (iii) localizing phase changes to the cone outer segment, where photoactivation occurs. Our method should have broad appeal for color vision applications in which the underlying neural processing of photoreceptors is sought and for investigations of retinal diseases that affect cone function.