Utility of PIP as a Novel Keratoconus Biomarker

PIP 作为新型圆锥角膜生物标志物的实用性

基本信息

批准号：
10245081
负责人：
Dimitrios Karamichos
金额：
$ 29.42万
依托单位：
UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
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：
2019-09-30 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10245081
关键词：
Address Adolescence Affect Age Agreement Animal Model Anterior uveitis Automobile Driving Basic Science Biological Biological Markers Blindness Blood Blood specimen Cells Clinical Clinical Research Collagen Computers Cornea Corneal Diseases Corneal Stroma Corneal dystrophy Data Denmark Descemet&apos s membrane Detection Development Diagnosis Diffuse Disease Down-Regulation Early Diagnosis Early treatment Ensure Epithelial Etiology Eye Injuries Female Fibroblasts Follow-Up Studies Foundations Fuchs&apos Endothelial Dystrophy Future Gender Genes Genetic Genetic study Glycoproteins Goals Human In Situ In Vitro Individual Keratoconus Keratoplasty Knowledge Left Life Liquid substance Longterm Follow-up Modality Myopia Non-Insulin-Dependent Diabetes Mellitus Norway Open-Angle Glaucoma Operative Surgical Procedures Pathogenesis Pathology Patient Care Patients Play Prevention Prolactin Proteins Public Health Publishing Quality of life Reading Reporting Research Research Personnel Role Route Saliva Sampling Serum Severities Shapes Specificity Systemic disease Thinness Time Tissues Uveitis Vision Visual Visual impairment Work base clinically relevant cohort corneal scar crosslink disability in vivo male malignant breast neoplasm novel novel diagnostics ocular surface potential biomarker programs protein expression rapid diagnosis recruit saliva sample skin disorder three dimensional cell culture tool

项目摘要

PROJECT SUMMARY/ABSTRACT Keratoconus (KC) is the most common corneal dystrophy, with adverse corneal changes that can dramatically affect vision. During KC progression, the cornea can show several pathologies, including fragmentation of Bowman’s layer, thinning of stroma and overlying epithelium, folds or breaks in Descemet’s membrane, and variable amounts of diffuse corneal scarring. Clinically, limited treatment options for KC patients include corneal transplantation and collagen cross-linking. Unfortunately, both corneal transplantation and collagen cross-linking have their own limitations. To date, the etiology and pathogenesis of KC remains unclear. As such, there is an urgent need to identify viable biomarker(s) that can help with the early diagnosis and treatment of KC. In 2014, we were the first to report the role and significant modulation of prolactin-induced protein (PIP) in vitro (3D cultures with human KC cells) and in vivo (human tear samples), and question its role during KC development and progression. Our preliminary data shows that PIP is significantly downregulated in KC patients when compared to Healthy individuals. Interestingly, downregulation of PIP was seen in three different human biological fluids: saliva, tears, and blood (serum). Furthermore, our preliminary data shows that PIP is not modulated in other relevant diseases, such as Uveitis and Type II Diabetes, suggesting potential specificity to KC. Even more strikingly, new data shows that PIP expression levels returned to normal on KC patients that had received corneal transplants. We posit that PIP can serve as a biomarker for KC onset and progression drive the development of future non-invasive treatment modalities. The current proposal is focused solely on PIP, with three main goals: 1) Cement PIP as a KC biomarker, 2) Determine the power and specificity of PIP, and 3) Determine PIP expression following known KC treatments. To ensure that we achieve our goals, we have assembled a large cohort of experts in the field from multiple clinical and research centers, as well as from the National Keratoconus Foundation (NKCF). Successful completion of the studies proposed will be a breakthrough in KC research and will alter current standards of care for patients with KC. Relevance to Public Health – KC is a major clinical problem resulting in visual impairment worldwide. There is an urgent need to develop novel diagnostic tools for the detection and treatment of KC in the early stages. Ultimately, the primary goal is to enable people with KC to live a normal life with little or no visual disability. The proposed work will move the field forward, is translational, clinically relevant, and in line with NEI’s program goals: “Apply the knowledge acquired from discoveries in the basic science of the cornea and other tissues of the ocular surface to the diagnosis, prevention, and treatment of ocular injury and disease”.

项目概要/摘要圆锥角膜 (KC) 是最常见的角膜营养不良，其不良角膜变化可显着在 KC 进展过程中，角膜会出现多种病变，包括角膜碎裂。鲍曼层、间质和上皮细胞变薄、后弹力层折叠或破裂，以及临床上，KC 患者的治疗选择有限，包括不同程度的弥漫性角膜疤痕。角膜移植和胶原蛋白交联不幸的是，角膜移植和胶原蛋白都存在。迄今为止，KC 的病因和发病机制仍不清楚。因此，迫切需要确定可行的生物标志物，以帮助早期诊断和治疗 2014年，我们首次报道了催乳素诱导的作用和显着调节作用。体外（人类 KC 细胞 3D 培养物）和体内（人类泪液样本）蛋白质 (PIP)，并质疑其作用我们的初步数据表明，在 KC 发育和进展过程中，PIP 显着下调。与健康个体相比，KC 患者的 PIP 下调在三人中出现。不同的人类生物体液：唾液、眼泪和血液（血清）此外，我们的初步数据表明。 PIP 在其他相关疾病（例如葡萄膜炎和 II 型糖尿病）中不受调节，这表明 PIP 具有潜在的潜力更引人注目的是，新数据表明 PIP 在 KC 上的表达水平恢复正常。我们认为 PIP 可以作为 KC 发病的生物标志物。和进展推动了未来非侵入性治疗方式的发展。该提案仅关注 PIP，具有三个主要目标：1) 水泥 PIP 作为 KC 生物标志物，2) 确定 PIP 的功效和特异性，以及 3) 确定已知 KC 处理后的 PIP 表达。我们实现了我们的目标，我们聚集了来自多个临床和领域的一大批专家研究中心以及国家圆锥角膜基金会 (NKCF) 的成功完成。拟议的研究将成为 KC 研究的突破，并将改变目前对患有以下疾病的患者的护理标准 K.C. 与公共卫生的相关性——KC 是导致全球视力障碍的一个主要临床问题。迫切需要开发新的诊断工具来早期检测和治疗 KC。最终，主要目标是使 KC 患者能够过上正常的生活，几乎没有或没有视力障碍。拟议的工作将推动该领域向前发展，具有转化性、临床相关性，并且符合 NEI 的计划目标：“应用从角膜和其他组织的基础科学发现中获得的知识眼表对眼损伤和疾病的诊断、预防和治疗”。