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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.

项目说明/摘要干眼病(DED)和其他眼表疾病(OSD)是导致视力下降的常见疾病功能和生活质量。常用的眼科防腐剂会导致中毒性上皮病结果导致OSD。这些疾病的治疗主要是通过使用姑息措施。太棒了有机会通过开发新的治疗方法来改善许多患者的生活质量。DED和OSD 与严重的角膜上皮功能障碍和眼表炎症改变有关。这些变化中的许多是由高渗透压、干燥和炎性侮辱引起的。组织蛋白是一个大家庭主要在唾液中发现的多肽，已知具有显著的伤口愈合和抗感染特性。关于组蛋白多肽的作用机制的数据很少，尽管一些作用被认为是通过未知的受体进行调节。我们发现这些多肽可以减轻炎症。有毒防腐剂暴露于眼表和实验条件下的变化是模仿DED的。我们还发现了一种潜在的新的组蛋白多肽的配体-受体相互作用。我们的龙学期目标是开发一种无毒和抗抑郁的新型DED和OSD疗法。煽动性的。我们的中心假设是，组蛋白多肽可以减轻有毒物质的炎症效应在体外和体内对角膜上皮细胞的炎性侮辱。我们将利用经过良好审查的有毒物质模型上皮病变、高渗和干燥以显示组蛋白多肽的治疗效果 OSD。我们还将进行研究，寻找组蛋白多肽的受体。建议的研究具有创新性。因为这是第一次研究组蛋白多肽在DED和OSD治疗中的应用。这些研究具有重要意义，因为它们将通过使用严格和在疾病的临床相关翻译模型中明确定义的方法和验证新的受体-配体两性关系。