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

Clusterin at the Ocular Surface

眼表面的聚集蛋白

基本信息

批准号：
9329433
负责人：
M. Elizabeth Fini
金额：
$ 51.61万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2018-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9329433
关键词：
Address Adverse effects Affect Aging Anti-Inflammatory Agents Anti-inflammatory Apical Basic Science Binding Biochemical Biological Assay Biological Response Modifier Therapy Blindness Cells Characteristics Clinical Contact Lenses Cornea Cyclosporine Cytoprotection Data Disease Drops Dry Eye Syndromes Environment Environmental Exposure Epithelial Epithelium Experimental Models Eye Galactose Binding Lectin Galectin 3 Genes Genetic Glycocalyx Glycoproteins Human Hydration status In Vitro Inflammation Inflammatory Journals Knockout Mice Knowledge Left Light Liquid substance Lubrication MMP9 gene Measurement Medical Medicine Methods Modeling Molecular Mus Nature Operative Surgical Procedures Ophthalmologic Surgical Procedures Pain Pathway interactions Patients Penetration Peptides Pharmaceutical Preparations Positioning Attribute Property Proteins Proteolysis Pruritus Publishing Redness Research Research Personnel Role Squamous Metaplasia Stress Structure Surface Symptoms Therapeutic Tissues United States Food and Drug Administration United States National Institutes of Health Work corneal epithelium corneal scar eye dryness in vivo inflammatory milieu innovation intercalation mouse model novel novel strategies novel therapeutics ocular surface prevent proteostasis response seal sulfated glycoprotein 2 tear proteins

项目摘要

7. PROJECT SUMMARY/ ABSTRACT Dry eye syndrome is a common affliction of the eye that affects millions of people. Dry eye is brought on by aging, eye surgery or environmental exposure and is also an adverse effect of contact lens wear, and topical eye medications. Symptoms include pain, burning, itching, redness, sensitivity to light and other discomfort. If left untreated, severe cases may result in vision loss due to corneal scarring. New research from this research team, recently published in the NIH-supported journal PLOS ONE, suggests a new approach to treating dry eye. Using an experimental mouse model, the researchers found that the natural tear protein known as clusterin selectively binds to the ocular surface barrier disrupted by desiccating stress in an all-or-none manner, while also preventing further damage. Known properties of clusterin suggest it may further protect against the upstream effects of inflammatory cascade activation and subsequent squamous metaplasia. The proposed research will investigate this previously unrecognized, endogenous protective mechanism. The planned studies make use of the mouse experimental model and a quantitative functional assay for ocular surface barrier disruption, and take advantage of mouse genetics. The specific aims are: 1) to determine the molecular nature of clusterin intercalation into the ocular surface glycocalyx, and how it might relate to the all- or-none effect; 2) to document the role of clusterin in anti-proteolysis, the effects of proteolysis on the capacity for clusterin binding, and the relationship between the proteolytic and clusterin pathways; 3) to define the endogenous clusterin protection pathway and its role in maintaining an anti-inflammatory environment at the ocular surface. The impact of this research will be new basic science knowledge about the ocular surface barrier, how it is altered in disease, and mechanisms of protection by clusterin. The results will set the stage for clinical innovation.

7. 项目摘要/摘要