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Modulators for Retinal Ganglion Cell Injury

视网膜神经节细胞损伤的调节剂

基本信息

批准号：
10355506
负责人：
ELDON E GEISERT
金额：
$ 48.07万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-01 至 2026-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10355506
关键词：
Activities of Daily Living Acute Adult Age American Anatomy Antibodies Binding Biological Markers Birth Blindness Cell Survival Cells Cessation of life ChIP-seq Classification Collaborations Collection Contrast Sensitivity Cornea Data Data Set Dendrites Detection Development Disease Drops Electroretinography Embryo Experimental Models Eye Eye Development Genes Genetic Genetic Transcription Glaucoma High-Throughput Nucleotide Sequencing Human Injections Injury Intervention Knock-out Knockout Mice Label Lead Link Measures Mediating Microspheres Modeling Molecular Monitor Morphology Mouse Strains Mus Nature Nerve Crush Optic Nerve Partner in relationship Pathway interactions Patients Pattern Pharmacology Phase Physiologic Intraocular Pressure Population Predisposition Proteins Research Design Resistance Retina Retinal Ganglion Cells Risk Risk Factors Role Structure Technology Testing Thick Variant Visual Visual Acuity base cell injury cell type chromatin immunoprecipitation directional cell experimental study ganglion cell genome wide association study improved magnetic beads mouse model novel outcome prediction rational design response retinal progenitor cell transcription factor

项目摘要

Summary The leading cause of blindness in Americans over the age of 60 is glaucoma. One risk factor for glaucoma is central corneal thickness. The thinner the cornea, the greater the risk of developing glaucoma. Recently, we have identified a transcription factor, POU6F2, that modulates central corneal thickness in the mouse and that is a risk factor for human glaucoma. The Pou6f2 knockout mouse has a thinner cornea than its wild-type littermates, while there is no apparent change in intraocular pressure. We propose that POU6F2 is expressed in novel subclasses of retinal ganglion cells (RGCs) that are sensitive to glaucomatous injury. Premise: Our four findings lead us to hypothesize that POU6F2 is in a transcriptional cascade responsible for the susceptibility and early death of a novel collection of ON-OFF directionally selective RGC subtypes. To test this hypothesis, we will focus on the role of POU6F2 in the response of RGCs in models of experimentally-induced and naturally- occurring glaucoma. The proposed experiments will uncover the POU6F2 molecular cascade that induces glaucomatous damage. We will relate our findings in the mouse to the human, through a collaboration with Dr. Janey Wiggs and the NEIGHBORHOOD consortium, interrogating the NEIGHBORHOOD meta-dataset to define molecular pathway associated with POU6F2 targets. We will determine if any of these downstream targets and their associated pathways represent factors for glaucoma risk. This basic understanding of the molecular interactions of POU6F2 will inform the rational design of strategies to improve detection of and therapy for glaucoma.

总结