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Mechanisms of retinal neuronal injury

视网膜神经元损伤的机制

基本信息

批准号：
8348385
负责人：
Wenbo Zhang
金额：
$ 36.67万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-30 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8348385
关键词：
Address Animal Model Animals Apoptosis Attenuated Blindness Blood Vessels Blood flow Bone Marrow Butyric Acids CXCL10 gene CXCL11 gene CXCL9 gene CXCR3 gene Cell Death Cells Cellular biology Cessation of life Clinical Data Development Diabetic Retinopathy Disease Endoplasmic Reticulum Extravasation Functional disorder Gene Deletion Genetic Glaucoma Healthcare Systems In Vitro Inflammation Inflammatory Injury Ischemia Leukocytes Life Stress Ligands Link Mediating Microglia Modeling Molecular Monitor Mus Neuronal Injury Neurons Optic Nerve Injuries Optical Coherence Tomography Outcome Study Oxidative Stress Oxidative Stress Induction Pathway interactions Patients Phase I Clinical Trials Physiologic Intraocular Pressure Production Proteins Quality Control Quality of life Reaction Reperfusion Therapy Reporting Retinal Retinal Diseases Retinal Ganglion Cells Retinal Vascular Occlusion Role Signal Transduction Site Testing Therapeutic Thick Tissues Up-Regulation Vision antiangiogenesis therapy cell injury chemokine receptor clinical Diagnosis clinical practice cytokine dehydroretinal design diabetic patient endoplasmic reticulum stress in vivo Model innovation monocyte mouse model neovascularization neuroprotection novel novel strategies prevent retinal ischemia retinal neuron tauroursodeoxycholic acid

项目摘要

DESCRIPTION (provided by applicant): Retinal neuronal death is a common pathological feature of many vision threatening diseases, such as diabetic retinopathy, retinal vascular occlusion, glaucoma, traumatic optic neuropathy, and others. These diseases can cause blindness, impair patients' quality of life, and stress our health care system. Retinal neuronal injury is a common pathological feature of these diseases. This study is to delineate the common mechanisms of neuronal injury during retinopathy and identify novel strategies to limit injury and preserve vision. We will use different models of retinal neuronal injury to test our novel hypothesis that endoplasmic reticulum (ER) stress- induced expression of CXCL10 has a key role in retinal neuronal damage due to CXCR3-mediated inflammatory reactions and induction of oxidative stress during retinopathy. We will use genetic and pharmacological approaches to address the following specific aims: 1) Determine the role of ER stress in increasing CXCL10 expression and retinal neuronal injury during retinopathy. 2) Investigate the role of CXCL10/CXCR3 in retinal neuronal injury during retinopathy. 3) Evaluate therapeutic benefits of neuroprotection by pharmacological blockade of ER stress or CXCR3. Outcomes from this study will provide novel common mechanisms of retinal neuronal injury and may be readily put into clinical practice for retinopathy. PUBLIC HEALTH RELEVANCE: ER stress is involved in tissue injury and CXCR3 is a chemokine receptor which has an essential role in inflammation, cell death, and anti-angiogenesis. This project is designed to understand whether and how ER- stress-induced activation of CXCR3 is involved in retinal neuronal injury in retinopathy and to investigate the therapeutic benefit by blocking ER stress and CXCR3.

描述（由申请人提供）：视网膜神经元死亡是许多视力威胁疾病的常见病理特征，如糖尿病视网膜病变、视网膜血管阻塞、青光眼、创伤性视神经病变等。这些疾病会导致失明，损害患者的生活质量，并给我们的医疗保健系统带来压力。视网膜神经元损伤是这些疾病的共同病理特征。本研究旨在阐明视网膜病变中神经元损伤的常见机制，并确定新的策略来限制损伤和保护视力。我们将使用不同的视网膜神经元损伤模型来检验我们的新假设，即内质网（ER）应激诱导的CXCL 10表达在视网膜病变期间由于CXCR 3介导的炎症反应和氧化应激诱导引起的视网膜神经元损伤中具有关键作用。我们将使用遗传学和药理学方法来解决以下具体目标：1）确定ER应激在视网膜病变期间增加CXCL 10表达和视网膜神经元损伤中的作用。2)研究CXCL 10/CXCR 3在视网膜病变过程中视网膜神经元损伤中的作用。3)评价通过药物阻断ER应激或CXCR 3的神经保护的治疗益处。本研究的结果将提供视网膜神经元损伤的新的常见机制，并可能很容易应用于视网膜病变的临床实践。公共卫生关系：ER应激参与组织损伤，CXCR 3是一种趋化因子受体，在炎症、细胞死亡和抗血管生成中起重要作用。该项目旨在了解ER应激诱导的CXCR 3激活是否以及如何参与视网膜病变中的视网膜神经元损伤，并研究通过阻断ER应激和CXCR 3的治疗益处。