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Single-Cell Transcriptomic Analysis of Human Retina

人类视网膜的单细胞转录组分析

基本信息

批准号：
10119528
负责人：
Mingyao Li
金额：
$ 41.35万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-05-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10119528
关键词：
Adult Affect Alabama Alzheimer&apos s Disease Alzheimer&apos s disease brain Alzheimer&apos s disease model Alzheimer&apos s disease pathology Alzheimer&apos s disease patient American Amyloid Proteins Amyloid beta-Protein Amyloid beta-Protein Precursor Anatomy Animal Model Animals Astrocytes Autopsy Axon Axonal Transport Biological Markers Blood Vessels Blood-Retinal Barrier Brain Cell Nucleus Cells Chromium Clinical Cognitive deficits Coupled Data Data Set Deposition Development Diagnosis Disease Progression Eye Eye Banks Funding Future Gene Expression Gene Expression Alteration Gene Expression Profile Genomics Geographic Locations Goals Histologic Homeostasis Hour Human Image Immune Individual Interneurons Location Maintenance Maps Measures Memory Loss Microglia Molecular Nerve Degeneration Neuraxis Neurodegenerative Disorders Neurofibrillary Tangles Neuroglia Neurons Optic Nerve Optical Coherence Tomography Parents Pathologic Patients Peripheral Photoreceptors Pilot Projects Play Population Recovery Regulation Research Retina Retinal Ganglion Cells Retinal macula Role Senile Plaques Spatial Distribution Structure Testing Thalamic structure Thinness Tissues Transcript Variant Visual cell type extracellular hyperphosphorylated tau macula nervous system disorder neuroinflammation response retinal nerve fiber layer retinal neuron screening single-cell RNA sequencing tau Proteins transcriptome sequencing transcriptomics vascular abnormality

项目摘要

PROJECT SUMMARY Alzheimer's Disease (AD) is a progressive neurodegenerative disease that affects 5.2 million Americans and 35 million worldwide. Pathologically, AD is characterized by deposits of extra-cellular amyloid plaques and neurofibrillary tangles. The retina and the brain have been found to be associated with a range of neurological diseases including AD and respond similarly to neuropathological conditions. Mounting evidence has suggested that AD also results in visual deficits, and pathological changes in the retinas of AD patients that include extensive loss of optic nerve and retinal ganglion cells, thinning of the retinal nerve fiber layer, and vascular abnormalities. As a projection of the central nervous system, the retina shares many cell types found in the brain including neurons, astrocytes, microglia, microvasculature, and a blood-retina barrier. Amyloid precursor protein is synthesized in retinal ganglion cells and is transported by the axons of the optic nerve to the brain. Additional proteins of the amyloid cascade are expressed by retinal neurons and glia. Further, amyloid beta plaques have been described in all retinal layers in animal models of AD. Histologically in humans, there is evidence of retinal thinning in AD patients and amyloid plaques in postmortem retinas of patients with early stage AD. Despite increasing evidence of retina involvement in AD, the underlying molecular and cellular mechanisms for these changes in the retina are still poorly understood. Another important factor in AD is the role of neuroinflammation. Although neuroinflammatory responses are commonly described in the brain of AD patients and animal models, only few studies have described retinal glia alterations in AD. In this project, we will test the hypothesis that measureable anatomical and molecular deficits occur in the retinas of individuals diagnosed with AD, and the retinal gene expression changes correlate with gene expression changes in the brain of individuals diagnosed with AD. Collaborating with the Alabama Eye Bank, the leader in rapid eye tissue recovery, we will perform single-cell RNA sequencing coupled to Spatial Transriptomics of the human retina in postmortem donors with AD, with the goal of identifying cells that are contributing to the development of AD pathology in the retina. Results from this pilot study will allow us to have a better understanding on the molecular and cellular variations of retinal changes in AD.

项目总结