Novel Treatments for Ocular Surface Diseases

眼表疾病的新疗法

基本信息

批准号：
10225306
负责人：
Vinay Aakalu
金额：
$ 38.78万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
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：
2019-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10225306
关键词：
Address Advanced Development Affect Animals Anti-Infective Agents Anti-Inflammatory Agents Autophagocytosis Benzalkonium Chloride Binding Binding Proteins Biological Assay Cell Culture Techniques Clinical Copper Cornea Custom Data Desiccation Development Disease Disease model Drug Formulations Dry Eye Syndromes Ensure Environment Enzymes Epithelial Exposure to Family Film Functional disorder Future G-Protein-Coupled Receptors Glaucoma Histidine Homeostasis Human Humidity IL8 gene In Vitro Inflammation Inflammation Mediators Inflammatory Interleukin-6 Lacrimal gland structure Ligands Mammalian Cell Matrix Metalloproteinases Measures Mediating Mediator of activation protein Metals Methods Modeling Mucositis Nickel Oral Osmolar Concentration Outcome Patients Peptide Hydrolases Peptides Pharmaceutical Preparations Physiological Production Property Proteins Protocols documentation Publishing Quality of life Research Saliva Stress System Testing Therapeutic Therapeutic Effect Toxic effect Toxicant exposure Vision antimicrobial antimicrobial peptide base clinically relevant corneal epithelium cytokine design experience experimental study histatin 1 histidine-rich proteins improved in vivo in vivo Model innovation lacrimal migration mouse model novel novel therapeutics ocular surface ophthalmic drug palliative receptor screening synthetic peptide translational model visual dysfunction wound healing

项目摘要

PROJECT DESCRIPTION/ABSTRACT Dry eye disease (DED) and other ocular surface diseases (OSD) are common conditions that can reduce visual function and quality of life. Commonly used ophthalmic preservatives can cause a toxic epitheliopathy that results in OSD. The treatment of these diseases is primarily through the use of palliative measures. Great opportunity exists to improve the quality of life of many patients by developing novel treatments. DED and OSD are associated with significant dysfunction of corneal epithelia and inflammatory changes on the ocular surface. Many of these changes are induced by hyperosmolarity, desiccation and inflammatory insults. Histatin is a family of peptides found primarily in saliva and is known to have significant wound healing and anti-infective properties. Little data exist on the mechanisms of action of histatin peptides, though some effects are thought to be mediated through as yet unknown receptors. We have found that these peptides can reduce inflammatory changes associated with exposures of toxic preservatives to the ocular surface and in experimental conditions that mimic DED. We have also found a potential novel ligand-receptor interaction for histatin peptides. Our long term objective is to develop a new class of DED and OSD therapeutics which are non-toxic and anti- inflammatory. Our central hypothesis is that histatin peptides can ameliorate the inflammatory effects of toxic and inflammatory insults to corneal epithelia in vitro and in vivo. We will utilize well vetted models of toxic epitheliopathy, hyperosmolarity and desiccation in order to show the efficacy of histatin peptides in treating OSDs. We will also undertake studies to find receptors for histatin peptide. The proposed research is innovative as it is the first study to investigate the use of histatin peptides in the treatment of DED and OSD. These studies are significant because they will advance the development of new therapeutics through the use of rigorous and well defined methods in clinically relevant translational models of disease and validate a novel receptor-ligand relationship.

项目描述/摘要干眼症（DED）和其他眼表疾病（OSD）是常见的疾病，可以减少视觉生活和生活质量。常用的眼科防腐剂可能会引起有毒的上皮病毒导致OSD。这些疾病的治疗主要是通过使用姑息治疗方法。伟大的存在通过开发新型治疗方法来改善许多患者生活质量的机会。 DED和OSD 与角膜上皮的明显功能障碍和眼部表面的炎症变化有关。这些变化中的许多是由高渗透性，干燥和炎症性侮辱引起的。 Histatin是一个家庭主要在唾液中发现的肽的肽，已知具有明显的伤口愈合和抗感染特性。关于组蛋白肽的作用机理的数据很少，尽管认为某些作用被认为是通过尚未知道的受体介导。我们发现这些肽可以减少炎症与在眼表面和实验条件下的有毒防腐剂暴露有关的变化那个模仿的ded。我们还发现了一种潜在的新型配体 - 受体相互作用，用于组蛋白肽。我们的漫长术语目标是开发一种新的DED和OSD治疗剂，它们无毒和抗炎症。我们的中心假设是，组织蛋白肽可以改善有毒的炎症作用在体外和体内对角膜上皮的炎症性侮辱。我们将利用审查良好的有毒模型上皮病，高渗色和干燥，以表明组蛋白肽在治疗中的疗效 OSDS。我们还将进行研究，以找到组蛋白肽的受体。拟议的研究是创新的因为这是首次研究组蛋白肽在DED和OSD治疗中的使用。这些研究之所以重要，是因为它们将通过使用严格的和在临床相关的疾病翻译模型中定义明确的方法，并验证一种新型的受体配体关系。