Therapeutic Corneal Cross-Linking Using Formaldehyde Releasing Agents

使用甲醛释放剂进行治疗性角膜交联

基本信息

批准号：
9106336
负责人：
DAVID C PAIK
金额：
$ 41.89万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-03-01 至 2020-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9106336
关键词：
Biological Assay Biological Markers Cells Chemicals Collagen Connective Tissue Cornea Cosmetics Debridement Development Disease Enzymes Epithelial Epithelium Equilibrium Excision Exposure to Eye Eyedrops Failure Formaldehyde Glutaral Goals Health Histologic Impaired wound healing In Situ Industry Infection Keratoconus Laser In Situ Keratomileusis Lasers Lead Life Mechanics Medical Methods Myopia Natural regeneration Outcome Pain Pathogenesis Patient Care Patients Permeability Photochemistry Play Procedures Process Progressive Myopia Property Protein-Lysine 6-Oxidase Proteins Reaction Retina Riboflavin Risk Role Safety Sclera Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Technology Testing Therapeutic Time Tissue Fixation Tissues Topical application Toxic effect Ultraviolet Rays Work base cancer risk chemical group corneal epithelium crosslink diagnostic biomarker human disease improved in vivo keratomileusis lens liquid chromatography mass spectrometry novel personal care products rapid growth research clinical testing simulation standard of care therapeutic biomarker therapy development

项目摘要

DESCRIPTION (provided by applicant): Although fixation of tissues using glutaraldehyde and formaldehyde have been a mainstay of numerous processes and procedures (i.e. histologic processing, etc.) related to medical practice in the past and present, inducing tissue cross-linking "in the patient" [Therapeutic Tissue Cross-linking (TXL)], for treating human disease, is novel. The rapid growth throughout the world of CXL (riboflavin photochemistry) in treating keratoconus (KC) and post-LASIK keratectasias (LASIK=Laser-Assisted in situ Keratomileusis) is proving that in vivo tissue cross-linking is possible and can be beneficial from a patient care standpoint. As good as it is, CXL has limitations, especially the need for debridement of the corneal epithelium (painful, infection risk, delayed healing, haze) and the use of ultraviolet (UV) light (with potential damage to the lens and retina, and even cancer risk). Our long-term goal is to develop therapies for human diseases through the use of in vivo therapeutic tissue cross-linking and to understand how enzymatic cross-linking contributes to the development of disease, specifically in KC. The overall objective of this particular application is to develop a nw treatment for corneal thinning diseases that will serve as a "springboard" for the development of similar treatments in other diseases (such as sclera in myopia, etc.). Formaldehyde releasing agents (FARs) are a promising group of chemical compounds, used widespread by the cosmetics industry as chemical preservatives in personal care products (PCPs). These FARs can be used for an alternative purpose, namely as therapeutic tissue cross-linking agents. The following aims will be pursued: 1. Using an ex vivo corneal cross-linking simulation set up that evaluates both cell toxicity and tissue fixation, establish optimal conditions for therapeutic corneal tissue cross-linking using FARs. 2. To test the hypothesis that topically applied FARs can induce corneal cross-linking in a safe and effective manner in the living eye. 3. To utilize analytical chemical methods (LC/MS and MALDI-TOF) to quantitate enzymatic collagen cross-links in keratoconus corneas and identify biomarkers of the induced cross-linking reactions (CXL and FARs). It is anticipated that these aims will yield: 1) A safe and effective method for inducing tissue cross- linking as a therapy for KC that leaves the epithelium intact and does not require use of UV light. 2) A deeper understanding of the role of enzymatic cross-linking in the pathogenesis of keratoconus as well as the development of new biomarkers for the therapeutic cross-linking reactions. Having the ability to cross-link the cornea using a topical cross-linking agent will "open the door" to applying this method to the treatment of other diseases in which mechanical tissue failure plays a role, including the sclera in progressive myopia.

描述（由适用提供）：尽管使用戊二醛和甲醛对组织的固定一直是与过去和现在有关的医学实践相关的多种过程和过程（即组织学处理等）的主导地位，诱导组织交叉链接“在患者中” [治疗性组织交叉链接（用于人类），用于治疗人类病，是针对人类的，是针对人类的，是针对人类疾病的。 CXL（核黄素光化学）在治疗角膜核（KC）和Lasik后角膜肌（Lasik = lasik =激光辅助原位角膜肌）方面的快速增长，这可能是在体内组织交叉链接可能是可能的，并且可以从患者护理人员的角度来看。尽管如此，CXL还是有局限性的，特别是需要调试角膜上皮（疼痛，感染风险，延迟愈合，雾霾）和使用紫外线（UV）光（对镜头和视网膜的潜在损害，甚至癌症风险）。我们的长期目标是通过使用体内治疗组织交联来开发人类疾病的疗法，并了解酶促交联如何有助于疾病的发展，特别是在KC中。该特定应用的总体目的是开发用于角膜稀疏疾病的NW治疗方法，该疾病将作为开发其他疾病类似治疗的“跳板”（例如在近视的巩膜等）。甲醛释放剂（FARS）是一组有前途的化合物，使用化妆品行业的宽度用作个人护理产品（PCP）的化学防腐剂。这些遥控器可用于替代目的，即作为治疗组织交联剂。将追求以下目的：1。使用离体角膜交联模拟，以评估细胞毒性和组织固定，为使用FARS提供治疗性角膜组织交联的最佳条件。 2。为了测试局部施加的远方的假设，可以在活眼中以安全有效的方式诱导角膜交联。 3。利用分析化学方法（LC/MS和MALDI-TOF）来定量角膜角膜角膜中的酶促胶原蛋白交联，并鉴定诱导的交联反应（CXL和FARS）的生物标志物。预计这些目标将产生：1）一种安全有效的组织交联方法作为KC的疗法，它使上皮完好无损，不需要使用紫外线。 2）更深入地了解酶联在角膜结构发病机理中的作用，以及用于治疗性交联反应的新生物标志物的发展。具有使用局部交联剂交联角膜的能力将“打开门”，将这种方法应用于处理机械组织衰竭起作用的其他疾病，其中包括渐进的近视中的巩膜。