Novel Treatments for Ocular Surface Diseases

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。

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.