Retinal Contributions to Vision Loss in Albinism

视网膜对白化病视力丧失的影响

• 批准号: 10464283
• 负责人: Joseph Carroll
• 金额: $ 61.43万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10464283
• 关键词: Abbreviations; Address; Albinism; Alleles; Anatomy; Angiography; Behavior; Behavioral; Blindness; Clinical; Color; Complex; Cone; Correlative Study; Data; Depth Perception; Development; Discrimination; Disease; Event; Eye; Fiber; Foundations; Functional Magnetic Resonance Imaging; Future; Ganglion Cell Layer; Genetic; Genotype; Goals; Hair; Health; Hereditary Disease; Human; Impairment; Individual; Interdisciplinary Study; Iris; Knowledge; Light; Link; Literature; Maps; Measurement; Melanins; Modeling; Molecular; Monophenol Monooxygenase; Morphology; Mosaicism; National Eye Institute; Neurons; Nuclear; Ocular Albinism; Oculocutaneous Albinism; Ophthalmoscopy; Optical Coherence Tomography; Outcome; Outcome Measure; Pathologic Nystagmus; Pathology; Patients; Phenotype; Photoreceptors; Photosensitivity; Physiological; Pigments; Prevalence; Privatization; Production; Publications; Quality of life; Recording of previous events; Refractive Errors; Reporting; Research Personnel; Resolution; Retina; Retinal Cone; Retinal Diseases; Retinal Ganglion Cells; Rod; Role; Scanning; Severities; Skin; Structure; Structure of retinal pigment epithelium; Technology; Testing; Therapeutic; Therapeutic Trials; Transillumination; Vision; Vision Disorders; Vision research; Visual; Visual Acuity; Visual system structure; Work; adaptive optics; adaptive optics scanning laser ophthalmoscopy; confocal imaging; density; fovea centralis; human subject; imaging approach; improved; individual patient; insight; interdisciplinary approach; interest; macula; multidisciplinary; non-invasive imaging; novel therapeutic intervention; optical imaging; patient population; programs; retinal imaging; retinal rods; tool

The fovea is arguably the most important part of the human retina. The normal fovea is characterized by an excavation of inner retinal layers (leaving behind the foveal pit and a concomitant avascular zone), an increased density of cone photoreceptors with nearly absent rods, and specialized “private line” circuitry between cones and midget retinal ganglion cells. Together, these specializations provide the basis for our high-acuity photopic vision. Patients with albinism have disrupted foveal anatomy, with visual deficits including variably reduced acuity, increased photosensitivity, high refractive errors, nystagmus, and impaired stereopsis. Despite the prevalence of albinism (~1 in 15,000), significant gaps remain in our understanding of the anatomical basis for the visual deficits in albinism. Such gaps not only compromise our ability to develop novel therapeutic strategies for patients with albinism but also fundamentally limit our understanding of how the retina interacts with central visual structures to determine key features of normal visual function. We have formed a multidisciplinary research team whose overall goal is to close these knowledge gaps through execution of the following specific aims: 1) Examine the influence of retinal melanin on visual acuity and the phenotypic spectrum of foveal morphology, 2) Characterize disruptions in foveal post-receptoral circuitry in subjects with albinism, and 3) Map rod photoreceptor mosaic topography in subjects with albinism. By advancing non-invasive imaging approaches that can reveal the physiological basis for visual deficits in albinism on a personalized basis, we gain access to outcome measures for use in emerging therapeutic trials and develop the ability to define the therapeutic potential for individual patients. Clinically, such approaches are broadly applicable to diseases beyond albinism. This work is also expected to have a significant positive impact by increasing our basic understanding of the relationships between melanin, foveal anatomy, photoreceptor topography, retinal circuitry, and visual function. These relationships inform the basic developmental and organizational principles of the human visual system. Importantly, our proposal directly addresses emerging needs outlined in the most recent publication from the National Eye Institute, “Vision Research: Needs, Gaps, & Opportunities”, and incorporates specific program objectives of the NEI Retinal Diseases Panel: (1) Characterize the macula and perifoveal regions of the retina to better understand the predilection of the macula for disease; (2) Improve understanding of the roles of neuronal activity and molecular events in the formation of central visual circuits during development; (3) Continue to develop and apply noninvasive technologies such as fMRI, OCT, adaptive optics, and confocal imaging to better understand retinal function and changes in disease states. Altogether, this project takes a multidisciplinary approach towards elucidating how retinal structures contribute to vision deficits and reduced quality of life in patients suffering from albinism and related vision disorders.

中央窝可以说是人类视网膜中最重要的部分。正常中央凹的特征是