Ocular Surface Histatins--Synthesis and Function

描述：(申请人摘要)组蛋白是一种小的阳离子多肽 存在于人类唾液中，表现出强大的抗真菌特性和 有助于口腔粘膜的非免疫(天生)保护。 口腔和口腔的结构、胚胎学和功能相似 眼部粘膜提示常见抗菌剂的发展 防御策略。这个实验室的初步研究首次 时间，显示结膜和结膜中均有组蛋白的存在 泪腺。 不同人群，包括免疫功能低下者、糖尿病患者和老年人 患者特别容易受到粘膜表面真菌感染的影响。 这些感染通常对标准疗法具有耐药性，在这种情况下， 眼表，会导致永久性失明。增强先天的能力 因此，粘膜防御能力是一种潜在的有效策略 控制和抗击这种感染。 我们建议用质量来鉴定和定量泪膜中的组蛋白。 光谱学。眼组织的原位杂交将允许- 组蛋白转录本的定位。细胞因子与微生物对人类的挑战 结膜细胞和随后的组蛋白转录本的定量 竞争性聚合酶链式反应将确定组蛋白的调控机制 抄写。最后，我们将量化唾液和泪液中的组蛋白 Sjogren‘s患者以确定自身免疫破坏的效果 腺体组织中这种抗真菌多肽的丰度。这些研究 将有助于开发创新的治疗策略，以 对抗眼组织中的真菌感染。

DESCRIPTION: (Applicant's Abstract) Histatins are small cationic peptides present in human saliva which exhibit potent antifungal properties and contribute to the non-immune (innate) protection of the oral mucosa. Structural, embryological, and functional similarities shared by oral and ocular mucosal membranes suggest the development of common antimicrobial defense strategies. Preliminary studies in this laboratory have, for the first time, demonstrated the presence of histatin in the both the conjunctiva and lacrimal gland. Diverse populations including the immunocompromised, diabetic and elderly patients are particularly susceptible to fungal infection of mucosal surfaces. These infections are often resistant to standard therapies and, in the case of the ocular surface, can lead to permanent loss of vision. Enhancement of innate mucosal defense capabilities is therefore a potentially effective strategy for controlling and combating such infections. We propose to identify and quantify the-histatin in tear film by mass spectroscopy. In situ hybridization of ocular tissues will allow for-the localization of histatin transcripts. Cytokine and microbial challenge to human conjunctival cells and subsequent quantification of histatin transcripts by competitive PCR will identify the regulatory mechanisms of histatin transcription. Lastly, we will quantify salivary and lacrimal histatin from Sjogren's patients in order to determine the effect of autoimmune destruction of glandular tissue on the abundance of this antifungal peptide. These studies will contribute to the development of innovative therapeutic strategies to combat fungal infection in ocular tissue.