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

Identification of genes responsible for glucocorticoid-induced glaucoma

糖皮质激素诱发青光眼基因的鉴定

基本信息

批准号：
8720007
负责人：
Weiming Mao
金额：
$ 17.76万
依托单位：
UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-01 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8720007
关键词：
Actins Affect Animals Anterior Aqueous Humor Biological Biological Markers Blindness Cattle Cell Culture Techniques Cells Characteristics Clinical Data Development Disease Eye Eye diseases Gene Expression Gene Expression Profiling General Population Genes Glaucoma Glucocorticoid Receptor Glucocorticoids Goals Health Human Knowledge Lead Mediating Medicine Mission Modeling Molecular Profiling Ocular Hypertension Open-Angle Glaucoma Pathogenesis Pathway interactions Patients Perfusion Phenotype Physiologic Intraocular Pressure Play Primary Open Angle Glaucoma Public Health Receptor Signaling Reporting Research Risk Role Sampling Signal Pathway Testing Therapeutic Effect Tissue Banks Tissues Trabecular meshwork structure Uncertainty Uveitis Vision Work base crosslink diabetic expectation gene discovery in vivo innovation macular edema myocilin novel optic nerve disorder overexpression response vector

项目摘要

DESCRIPTION (provided by applicant): Glucocorticoid (GC)-induced ocular hypertension (OHT) and glaucoma (GIG) occurs in 30-40% of the general population. The susceptible people are called GC-responders while the others are called non-responders. Although this ocular disease has been studied for decades, there is a fundamental gap in understanding the disease mechanism. Therefore, the long-term goal of this project is to elucidate the pathways and their components in the trabecular meshwork (TM) that mediate GC-induced OHT and GIG. The objective in this application is to determine the key TM genes that are responsible for GC-induced OHT and GIG. The central hypothesis, based on the fact that GIG is genetically determined, is that a select set of genes in the TM is responsible for GC-induced OHT and GIG. The rationale for this study is that the understanding of GIG helps to develop novel GCs with less potential of inducing GIG as well as better therapeutic effects. In addition, the knowledge of GIG will help us to understand primary open angle glaucoma because they share extensive similarities. Guided by strong preliminary data, this hypothesis will be tested by pursuing two specific aims: 1) identify the genes that are differentially expressed or regulated in GC-responder and non-responder bovine TM (BTM) cells/tissues; and 2) determine the role of the genes identified (from SA#1) in GC responsiveness and GC-induced OHT. Under the 1st aim, an already constructed bovine anterior segment perfusion culture model will be used to establish/collect BTM cells and tissues from GC-responder and non-responder eyes. By comparison of gene expression profiles between GC-responders and non-responders, the genes that are differentially expressed will be selected as candidates for GIG. Under the 2nd aim, the candidates from SA#1 will be manipulated in BTM cell cultures and perfusion cultured bovine eyes to determine whether they mediate GC-induced biological effects. This project is significant, because it will elucidate the key factors that determine GC-induced OHT and GIG. The approach is innovative, because TM cells/tissues with clearly defined and recorded IOP response to GCs will be used for gene expression profiling. Ultimately, the discovery of these key factors will no doubt help to better understand this vision-threatening disease. They will serve as a guide for further research in the human eye as well as biomarkers for the development of safer GCs.

描述（由申请人提供）：糖皮质激素（GC）引起的高眼压（OHT）和青光眼（GIG）发生在30-40%的普通人群中。易感人群被称为气相色谱反应者，而其他人被称为无反应者。虽然这种眼部疾病已经研究了几十年，但在了解疾病机制方面存在根本性的差距。因此，本项目的长期目标是阐明小梁网（TM）中介导gc诱导的OHT和GIG的通路及其组成。本应用程序的目的是确定负责gc诱导OHT和GIG的关键TM基因。基于GIG是由基因决定的这一事实，核心假设是TM中的一组精选基因负责gc诱导的OHT和GIG。本研究的基本原理是，对GIG的理解有助于开发新的GCs，这些GCs诱导GIG的潜力更小，治疗效果更好。此外，知识