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:
- 金额:$ 39.98万
- 依托单位:
- 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:
- 关键词:AddressAdvanced DevelopmentAffectAnimalsAnti-Infective AgentsAnti-Inflammatory AgentsAutophagocytosisBenzalkonium ChlorideBindingBinding ProteinsBiological AssayCell Culture TechniquesClinicalCopperCorneaCustomDataDesiccationDevelopmentDiseaseDisease modelDrug FormulationsEnsureEnvironmentEnzymesEpithelialEpitheliumExposure toEye diseasesFamilyFilmFunctional disorderFutureG-Protein-Coupled ReceptorsGlaucomaHistidineHomeostasisHumanHumidityIL8 geneIn VitroInflammationInflammation MediatorsInflammatoryInterleukin-6Lacrimal gland structureLigandsMammalian CellMatrix MetalloproteinasesMeasuresMediatingMediator of activation proteinMetalsMethodsModelingMucositisNickelOralOsmolar ConcentrationOutcomePatientsPeptide HydrolasesPeptidesPharmaceutical PreparationsPhysiologicalProductionPropertyProteinsProtocols documentationPublishingQuality of lifeResearchSalivaStressSystemTestingTherapeuticTherapeutic EffectToxic effectToxicant exposureVisionVisualantimicrobialantimicrobial peptidebaseclinically relevantcorneal epitheliumcytokinedesignexperienceexperimental studyeye drynesshistatin 1histidine-rich proteinsimprovedin vivoin vivo Modelinnovationlacrimalmigrationmouse modelnovelnovel therapeuticsocular surfaceophthalmic drugpalliativereceptorscreeningsynthetic peptidetranslational modelwound 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)是可降低视觉刺激的常见病症。
功能和生活质量。常用的眼科防腐剂可引起毒性上皮病,
导致OSD。这些疾病的治疗主要是通过使用姑息措施。伟大
存在通过开发新的治疗来改善许多患者的生活质量的机会。DED和OSD
与角膜上皮的显著功能障碍和眼表的炎性变化有关。
这些变化中的许多是由高渗、干燥和炎症损伤引起的。组胺素是一个家族
主要存在于唾液中的肽,已知具有显著的伤口愈合和抗感染特性。
关于组胺素肽的作用机制的数据很少,尽管一些作用被认为是
通过未知的受体介导。我们已经发现这些肽可以减少炎症反应,
与眼表和实验条件下有毒防腐剂暴露相关的变化
模仿DED我们还发现了一个潜在的新的组胺素肽配体-受体相互作用。我们漫长
长期目标是开发一类新的DED和OSD治疗剂,它们是无毒的,
煽动性我们的中心假设是,组胺素肽可以减轻毒性的炎症反应,
以及在体外和体内对角膜上皮的炎性损伤。我们将使用经过严格审查的有毒模型
为了显示组胺素肽在治疗上皮病、高渗和干燥中的功效,
OSDs。我们还将进行研究,寻找组胺素肽的受体。该研究具有创新性
因为这是首次研究组胺素肽在治疗DED和OSD中的用途。这些研究
是重要的,因为它们将通过使用严格的,
在疾病的临床相关转化模型中定义明确的方法,并验证新型受体-配体
关系
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Vinay Aakalu其他文献
Vinay Aakalu的其他文献
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{{ truncateString('Vinay Aakalu', 18)}}的其他基金
Novel Treatments for Modulation of Innate Immunity in Veteran Related Eye Diseases
调节退伍军人相关眼病先天免疫的新疗法
- 批准号:
9562360 - 财政年份:2018
- 资助金额:
$ 39.98万 - 项目类别:
Novel Treatments for Modulation of Innate Immunity in Veteran Related Eye Diseases
调节退伍军人相关眼病先天免疫的新疗法
- 批准号:
10292904 - 财政年份:2018
- 资助金额:
$ 39.98万 - 项目类别:
Novel Treatments for Modulation of Innate Immunity in Veteran Related Eye Diseases
调节退伍军人相关眼病先天免疫的新疗法
- 批准号:
10046282 - 财政年份:2018
- 资助金额:
$ 39.98万 - 项目类别:
Novel Treatments for Modulation of Innate Immunity in Veteran Related Eye Diseases
调节退伍军人相关眼病先天免疫的新疗法
- 批准号:
10516064 - 财政年份:2018
- 资助金额:
$ 39.98万 - 项目类别:
Study of Accessory Lacrimal Gland and Precursor Cell Biology
副泪腺及前体细胞生物学研究
- 批准号:
9044784 - 财政年份:2014
- 资助金额:
$ 39.98万 - 项目类别:
Study of Accessory Lacrimal Gland and Precursor Cell Biology
副泪腺及前体细胞生物学研究
- 批准号:
8679183 - 财政年份:2014
- 资助金额:
$ 39.98万 - 项目类别:
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