Ocular Surface Histatins--Synthesis and Function

描述：（申请人的摘要）组胺素是小的阳离子肽 存在于人类唾液中，表现出有效的抗真菌特性， 有助于口腔粘膜的非免疫（先天）保护。 口腔和哺乳动物在结构、胚胎学和功能上的相似性， 眼粘膜表明， 防御战略。这个实验室的初步研究表明， 时间，证明了在结膜和 泪腺 不同人群，包括免疫功能低下、糖尿病和老年人 患者对粘膜表面的真菌感染特别敏感。 这些感染通常对标准疗法有抵抗力， 眼表的损伤会导致永久性的视力丧失。增强先天 因此，粘膜防御能力是一种潜在的有效策略， 控制和防治这些感染。 我们建议通过质量来鉴定和定量泪膜中的-组胺素 谱眼组织的原位杂交将允许 组胺素转录物的定位。细胞因子和人体微生物挑战 结膜细胞和随后的定量组胺素转录本， 竞争性PCR将确定组胺素的调节机制 转录。最后，我们将量化唾液和泪液组胺， 为了确定自身免疫性破坏的效果， 腺组织中抗真菌肽的丰度。这些研究 将有助于开发创新的治疗策略， 对抗眼部组织的真菌感染。

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.