Novel Treatments for Ocular Surface Diseases

眼表疾病的新疗法

基本信息

批准号：
9902473
负责人：
Vinay Aakalu
金额：
$ 39.98万
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/9902473
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 Ensure Environment Enzymes Epithelial Epithelium Exposure to Eye diseases 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 Visual antimicrobial antimicrobial peptide base clinically relevant corneal epithelium cytokine design experience experimental study eye dryness 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 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/摘要干眼病 (DED) 和其他眼表疾病 (OSD) 是导致视力下降的常见病症功能和生活质量。常用的眼科防腐剂可引起中毒性上皮病，结果显示在 OSD 中。这些疾病的治疗主要是通过使用姑息措施。伟大的通过开发新的治疗方法来改善许多患者的生活质量是存在的。 DED 和 OSD 与角膜上皮的显着功能障碍和眼表面的炎症变化有关。许多这些变化是由高渗透压、干燥和炎症损伤引起的。组蛋白是一个家族主要存在于唾液中的肽，已知具有显着的伤口愈合和抗感染特性。关于组蛋白肽作用机制的数据很少，尽管一些作用被认为是通过迄今未知的受体介导。我们发现这些肽可以减少炎症与有毒防腐剂暴露于眼表和实验条件相关的变化模仿 DED。我们还发现了组蛋白肽的潜在新型配体-受体相互作用。我们的长长期目标是开发一类新的 DED 和 OSD 疗法，它们无毒且抗炎症。我们的中心假设是组氨酸肽可以改善有毒物质的炎症作用以及体外和体内对角膜上皮的炎症损伤。我们将利用经过严格审查的有毒模型上皮病、高渗性和干燥，以显示组蛋白肽在治疗中的功效 OSD。我们还将开展研究以寻找组蛋白肽的受体。所提出的研究具有创新性因为这是第一项研究组蛋白肽在 DED 和 OSD 治疗中的应用。这些研究意义重大，因为它们将通过使用严格和可靠的方法来推动新疗法的开发在临床相关疾病转化模型中明确的方法并验证新型受体-配体关系。