Investigating fundamental properties and clinical applications of the optoretinogram

研究视视网膜图的基本特性和临床应用

• 批准号: 10357416
• 负责人: Ravi S. Jonnal
• 金额: $ 37.28万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10357416
• 关键词: 3-Dimensional; Affect; Age related macular degeneration; Animal Model; Biochemical; Biochemical Process; Biological Assay; Blindness; Brain; Cells; Characteristics; Clinic; Clinical; Clinical Trials; Complex; Data; Data Analyses; Dependence; Development; Disease; Duct (organ) structure; Early Diagnosis; Electroretinography; Feedback; Functional disorder; Genetic Models; Goals; Grant; Health; Human; Image; Interneurons; Lead; Light; Measurable; Measurement; Measures; Methods; Microscopic; Morphology; Mutation; Natural experiment; Neuronal Dysfunction; Neurophysiology - biologic function; Noise; Optical Coherence Tomography; Optics; Pathologic; Pathology; Pathway interactions; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Photons; Photoreceptors; Physiology; Property; Proteins; Public Health; Reproducibility; Resolution; Rest; Retina; Retinal Diseases; Rod Outer Segments; Sampling; Secondary to; Sex Differences; Signal Transduction; Source; Stimulus; Techniques; Technology; Testing; Three-Dimensional Image; Tissues; Transducin; Translations; Variant; Vertebrate Photoreceptors; Visual Acuity; Work; adaptive optics; age effect; base; cell injury; clinical application; clinical imaging; design; disorder of macula of retina; genetic testing; geographic atrophy; improved; inherited retinal degeneration; interest; mouse model; novel; response; retinal neuron; tool

Abstract This grant will investigate the optoretinogram (ORG)–an experimental, all optical assay of human photoreceptor function–and its potential to reveal dysfunction at the cellular level. The ORG is based on adaptive optics optical coherence tomography (AO­OCT), which is the only existing way to produce 3D images of the living human retina with cellular resolution. It leverage our novel observation that light stimuli cause microscopic deformations in the living photoreceptor outer segment (OS), along with OCT’s sensitivity to deformations in the tissue much smaller than the wavelength of the imaging source. Aim 1 investigates the ORG’s ability to measure function in rods and cones, by measuring responses in normal subjects and characterizing the signal’s sensitivity to changes in stimu­ lus energy, and factors affecting this sensitivity, such as spatial and temporal variance in response, computational factors, and photon noise. Aim 2 investigates the mechanisms underlying light­evoked OS deformation. We will rigorously determine the light levels at which the deformations are saturated, the effect of multiple flashes, and the signal’s dependence on retinal eccentricity, all of which provide valuable information about the biochemical processes causing the observed deformations. Aim 3 applies the ORG to well­characterized retinal disease, to determine whether it is able to detect pathological dysfunction in photoreceptors suffering from known deficits. Well­characterized deficits, in turn, offer natural experiments which may shed light on the biochemical and biome­ chanical determinants of the observed light­evoked deformations in the OS.

摘要