Regulatory roles for collagen XII in establishment of corneal stromal structure and function and re-establishment after injury

胶原蛋白 XII 在角膜基质结构和功能的建立以及损伤后重建中的调节作用

• 批准号: 10468032
• 负责人: Edgar Mauricio Espana
• 金额: $ 36.25万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10468032
• 关键词: Address; Adult; Americas; Anterior; Apoptosis; Blindness; Chemical Injury; Cicatrix; Collagen; Cornea; Corneal Stroma; Coupled; Data; Deposition; Deterioration; Development; Disease; Environment; Extracellular Matrix; Foundations; Gender; Goals; Homeostasis; Human; Injections; Injury; Keratitis; Keratoplasty; Knockout Mice; Laceration; Mediating; Medical; Modeling; Mus; Myofibroblast; Natural regeneration; Operative Surgical Procedures; Pathway Analysis; Patients; Pattern; Pharmacologic Substance; Phase; Regulation; Role; Secondary to; Stromal Cells; Structure; Testing; Therapeutic Intervention; Thick; Tissue Engineering; Tissues; Transplantation; Traumatic injury; Up-Regulation; Vision; biomechanical test; cell behavior; corneal epithelial wound healing; corneal scar; healing; improved; innovation; insight; interest; light scattering; mouse model; novel; prevent; preventive intervention; small hairpin RNA; therapeutic development; tissue regeneration; wound; wound healing; wound response

PROJECT SUMMARY/ABSTRACT This application addresses the general hypothesis that collagen XII is essential for the acquisition of corneal stroma structure and function, and for reacquisition after injury. The concept that collagen XII modulates stromal wound healing is innovative and opens multiple translational prospects. Scar amelioration is noted during wound healing in the absence of collagen XII. Our overall goal is to provide a foundation to develop applications for matrix deposition manipulation during wound healing, and provide a rational basis for pharmaceutical and surgical therapeutic interventions aimed at promoting scarless stromal regeneration. The specific aims are to: (1) elucidate the regulatory roles of collagen XII in the acquisition of stromal structure and function; (2) determine the mechanism(s) whereby collagen XII regulates stromal wound healing; and (3) identify therapeutic interventions involving modulation of collagen XII to decrease human stromal scar formation during wound healing. The aims will test the hypotheses that: (1) differential and regulated expression of collagen XII is a critical mechanism required for acquisition of stromal structure and function; (2) collagen XII expression patterns observed in development and maturation are recapitulated during adult stromal wound healing to regulate stromal healing and scar formation; and (3) down-regulating collagen XII expression favors stromal regeneration over scarring. Therefore, modulation of collagen XII expression will have a positive impact on the reacquisition of normal stromal structure and function. This proposal will have significant impact, providing critical information for the development of novel medical and surgical therapies for patients with stromal scars, by far the most common indication for anterior lamellar and penetrating full thickness transplantation in America.

项目摘要/摘要 这项应用解决了XII胶原蛋白对获得角膜必不可少的普遍假设 基质的结构和功能，以及损伤后的再获得。XII胶原蛋白调控的概念 基质伤口愈合是创新的，并开辟了多种翻译前景。疤痕改善值得注意 在伤口愈合期间，在没有XII胶原的情况下。我们的总目标是为发展提供基础 在伤口愈合过程中应用基质沉积操作，并提供合理的基础 旨在促进无疤痕基质再生的药物和外科治疗干预措施。这个 其具体目的是：(1)阐明XII胶原在基质结构和细胞周期中的调节作用。 功能；(2)确定XII胶原蛋白调节基质伤口愈合的机制(S)；以及(3) 确定涉及调节XII胶原以减少人间质瘢痕的治疗干预措施 在伤口愈合过程中形成。这些目标将检验以下假设：(1)差别和监管 XII胶原蛋白的表达是获得基质结构和功能所必需的关键机制； 在发育和成熟过程中观察到的XII胶原蛋白的表达模式在成年时被概括。 基质伤口愈合调节基质愈合和瘢痕形成；以及(3)下调XII胶原蛋白 表情有利于基质再生而不是疤痕形成。因此，对XII胶原蛋白表达的调控将 对重新获得正常的间质结构和功能有积极的影响。这项建议将会有 重大影响，为开发新的内科和外科疗法提供关键信息 对于有基质瘢痕的患者，到目前为止最常见的适应症是前板层和穿透性全瘢痕。 美国的厚度移植。

项目成果

Stromal microsporidial keratitis successfully treated with medical therapy.

• DOI: 10.1016/j.ajoc.2021.101178
• 发表时间: 2021-09
• 期刊: American journal of ophthalmology case reports
• 作者: Donovan CP;Margo CE;Espana EM
• 通讯作者: Espana EM

Fungal keratitis: Mechanisms of infection and management strategies.

• DOI: 10.1016/j.survophthal.2021.08.002
• 发表时间: 2022-05
• 期刊: SURVEY OF OPHTHALMOLOGY
• 影响因子: 5.1
• 作者: Donovan, Christopher;Arenas, Eduardo;Ayyala, Ramesh S;Margo, Curtis E;Espana, Edgar M
• 通讯作者: Espana, Edgar M

Collagen XII regulates stromal wound closure.

XII 胶原蛋白调节基质伤口闭合。

• DOI: 10.1016/j.exer.2023.109456
• 发表时间: 2023
• 期刊: Experimental eye research
• 影响因子: 3.4
• 作者: Donovan,Christopher;Cogswell,Devon;Sun,Mei;Adams,Sheila;Avila,MarcelY;Margo,CurtisE;Koch,Manuel;Espana,EdgarM
• 通讯作者: Espana,EdgarM

Genipin increases extracellular matrix synthesis preventing corneal perforation.

• DOI: 10.1016/j.jtos.2023.02.003
• 发表时间: 2023-03
• 期刊: The ocular surface
• 作者: Cristopher Donovan;Mei Sun;Devon Cogswell;C. Margo;M. Ávila;E. Espana

Diseases of the corneal endothelium.

• DOI: 10.1016/j.exer.2021.108495
• 发表时间: 2021-04
• 期刊: Experimental eye research
• 影响因子: 3.4
• 作者: Jeang LJ;Margo CE;Espana EM
• 通讯作者: Espana EM