权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Pigment Regeneration Mechanisms in the Human Retina

人类视网膜色素再生机制

基本信息

批准号：
10671007
负责人：
Frans Vinberg
金额：
$ 39.66万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-30 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10671007
关键词：
Affect Age Age related macular degeneration Aging Animal Model Animals Automobile Driving Autopsy Biochemical Reaction Biological Models Biology Blindness Cells Collaborations Color Visions Cone Critical Pathways Dark Adaptation Darkness Disease Dryness Elderly Electrodes Electrophysiology (science)Electroretinography Environment Eye Eye Banks Face Geographic Locations Goals Health Hour Human Individual Isomerism Kinetics Knowledge Light Light Adaptations Lighting Maintenance Measures Mediating Methods Molecular Muller&apos s cell Mus National Eye Institute Natural regeneration Neural Retina Organ Organ Donor Panthera leo Pathogenesis Pathway interactions Peripheral Photons Photophobia Photoreceptors Pigment Epithelium Pigments Primates Process Protocols documentation Reading Regenerative pathway Research Retina Retinal Cone Retinal Pigments Rod Rodent Role Salamander Sampling Strategic Planning Structure of retinal pigment epithelium Suction Sunlight Techniques Testing Time Tissue Donors Tissues Transportation Utah Vertebrate Photoreceptors Vision Vision research Work disorder of macula of retina effective therapy experience experimental study fovea centralis human disease improved insight macula macular dystrophy nonhuman primate prevent response tissue preparation visual cycle

项目摘要

ABSTRACT During the past 2-3 decades important work has been done to resolve the mechanisms of light and dark adaptation as well as disease in the mammalian rod and cone photoreceptors using mouse as a model system. However, the mouse is a nocturnal animal that lacks the macula, a specialized central region in primate retina that provides high-acuity color vision critical for human everyday survival. Consequently, mechanisms of human daytime vision or diseases that disrupt photoreceptors in the macula, such as Age-Related Macular Degeneration (AMD), are challenging to study in mice. For example, there is no effective treatment for the dry form of AMD, the most common cause of blindness among the elderly. Thus, there is a critical need to better understand the biology of the photoreceptors in the human macula in health and disease. This is particularly true of cone photoreceptors compared to rods that have been more extensively studied. Recent studies have established both light-independent and light-dependent pigment regeneration pathways within the mouse retina isolated from the pigment epithelium (RPE). These pathways regenerate pigment via Müller cells in cone-specific pathways (light-independent and -dependent intraretinal visual cycles) or in the photoreceptor cells themselves by a cell-autonomous regeneration mechanism. However, nothing is known about these mechanisms in the human macula or fovea. The goal of this proposal is to determine the contribution of the RPE-independent pigment regeneration pathways to the ability of cones to dark adapt quickly and maintain sensitivity in bright light specifically in the human macula. Our central hypothesis is that the canonical visual cycle that operates via the RPE is too slow to maintain vision in bright light or mediate dark adaptation during rapidly changing levels of illumination in the human macula. The work is organized into two specific aims. These are to determine the contribution of the light-independent intraretinal visual cycle (Aim I) and photic pigment regeneration pathways (Aim II) to dark adaptation and maintenance of light sensitivity of human macular cones. The experiments will employ ex vivo electroretinography and single cell suction electrode recordings. These techniques are well suited for assessing the role of visual cycles and cell-autonomous pigment regeneration pathways in dark adaptation and maintenance of light sensitivity, respectively. We will leverage our experience and collaborations with Eye Banks that we have established during the past three years to develop donor criteria and protocols to record light-evoked responses of macular cones from organ or research donor human eyes 1 – 5 hours postmortem. Results of these studies will determine the contribution of different visual cycle pathways to human vision mediated by the cones across geographical regions of the retina, including the fovea. This information will provide a basis for studies to elucidate pathogenesis of macular dystrophies and potential targets to improve vision or prevent vision loss in aging or diseased human eye.

摘要