Dietary Supplement of n-3 PUFA to Control Corneal Inflammation

膳食补充剂 n-3 PUFA 控制角膜炎症

• 批准号: 10393908
• 负责人: Dimitrios Karamichos
• 金额: $ 15.31万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10393908
• 关键词: 3-Dimensional; Area; Blindness; Burn injury; Ceramides; Chemicals; Chronic; Cicatrix; Complex; Contact Lenses; Cornea; Corneal Abrasion; Corneal Diseases; Corneal Injury; Corneal Neovascularization; Corneal Opacity; Corneal dystrophy; Data; Development; Diet; Dietary Supplementation; Docosahexaenoic Acids; Due Process; Economics; Eicosapentaenoic Acid; Equilibrium; Extracellular Matrix; Eye; FDA approved; Feedback; Fibroblasts; Fibrosis; Fish Oils; G-Protein-Coupled Receptors; GTP-Binding Protein alpha Subunits, Gs; Genetic; Genetic Diseases; Genetic Transcription; Human; Infection; Inflammation; Investigation; Keratoconus; Keratoplasty; Knock-out; Mediator of activation protein; Metabolism; Mus; Myofibroblast; N-3 polyunsaturated fatty acid; Operative Surgical Procedures; Oral; Outcome; Pathologic; Pathway interactions; Patients; Pharmaceutical Preparations; Phenotype; Play; Process; Protein Isoforms; Puncture wound; Research; Resolution; Role; SPHK1 enzyme; Signal Pathway; Signal Transduction; Site; Sphingolipids; Sphingosine; Sphingosine-1-Phosphate Receptor; Stromal Cells; Systemic disease; Testing; Therapeutic; Tissues; Transcriptional Activation; Transforming Growth Factor beta Receptors; Transforming Growth Factors; Translating; Transplantation Surgery; Trauma; United States National Institutes of Health; Up-Regulation; Wild Type Mouse; corneal epithelial wound healing; corneal regeneration; corneal scar; dietary supplements; effective therapy; fibrogenesis; healing; human disease; improved; in vitro Model; in vivo; inhibitor/antagonist; lipid mediator; migration; mouse model; neovascularization; new therapeutic target; novel; parent grant; prevent; receptor; response; sight restoration; small molecule inhibitor; sphingosine 1-phosphate; therapeutic development; wound healing

Title: Dietary Supplement of n-3 PUFA to Control Corneal Inflammation Abstract: Cornea being the outer most tissue in the eye suffers regular injuries from corneal abrasions, puncture wounds, chemical and thermal burns that induce corneal inflammation. Corneal inflammation is also integral to genetic diseases like keratoconus, long-term wearing of contact lenses, and surgical corneal transplantation. Imbalances in inflammation and improper wound-healing (resolution) causes corneal scar and neovascularization (NV) that leads to blindness. Up to one fourth of all cases of blindness worldwide are attributable to corneal opacities generated by scarring, or fibrosis, representing a huge economic and societal burden. The primary cause of corneal fibrosis development is defective wound healing process due to imbalances in the inflammation and its resolution. Currently, there is no FDA-approved drug that facilitates proper corneal wound healing. We hypothesize that n-3 polyunsaturated fatty acids (PUFAs) from Fish Oil dietary supplementation will inhibit corneal fibrosis and NV by reducing chronic inflammation and augmenting resolution and wound-healing. During inflammation and tissue healing, it is the N-3 PUFAs (such as eicosapentaenoic acid, EPA, and docosahexaenoic acid, DHA) that generates several bioactive lipid mediators (such as resolvins, neuroprotectins and maresins) that play essential roles in resolution of inflammation and tissue healing. Although substantial research data is available regarding the benefits of n-3 PUFAs (DHA and EPA) in many human systemic diseases, the role of n-3 PUFAs in corneal healing and restoration of vision has not been studied. We propose to determine the efficacy of dietary supplementation of n-3 PUFA from OmegaRx2 Fish Oil (Zone Labs) to prevent corneal scar and NV in mouse model of corneal injuries. We anticipate our study will ultimately translate in to human augmentative dietary supplement of n-3 PUFAs to help balance the inflammation and improve the resolution and wound-healing in the corneas that are prone to develop scar and NV due to underlying genetic causes, contact lens wearing or corneal transplantation surgery and thus will prevent formation of permanent scar and blindness.

标题：N-3 PUFA的饮食补充以控制角膜炎症 摘要：角膜是眼睛中最外部的组织，遭受角膜擦伤，穿刺的常规伤害 伤口，化学和热燃烧会诱发角膜炎症。角膜炎症也是不可或缺的 诸如圆锥角膜，长期佩戴隐形眼镜和手术角膜移植等遗传疾病。 炎症和伤口治疗不当（分辨率）的失衡会导致角膜疤痕和 新生血管形成（NV），导致失明。全世界所有失明案件中最多四分之一是 归因于疤痕或纤维化产生的角膜泥泞，代表了巨大的经济和社会 负担。角膜纤维化发育的主要原因是由于 炎症及其解决方案的失衡。目前，没有FDA批准的药物可以促进适当的 角膜伤口愈合。我们假设鱼油饮食中的N-3多不饱和脂肪酸（PUFA） 补充将通过减少慢性炎症和增强来抑制角膜纤维化和NV 分辨率和伤口愈合。 在炎症和组织愈合过程中，它是N-3 PUFA（例如Eicosapentaenoic Acid，EPA和 Docosahexaenoic，DHA），生成多个生物活性脂质介质（例如Resolvins，NeuroProtectins 和海素）在炎症和组织愈合方面起着重要作用。虽然很重要 在许多人类的系统中，可获得有关N-3 PUFA（DHA和EPA）的好处的研究数据 疾病，N-3 PUFA在角膜愈合和视力恢复中的作用尚未被研究。我们建议 确定从欧米咖啡鱼油（区域实验室）饮食补充N-3 PUFA的功效（区域实验室） 为了防止角膜损伤的小鼠模型中的角膜疤痕和NV。我们预计我们的研究最终将 转化为N-3 PUFA的人类增强饮食补充剂，以帮助平衡炎症和 改善角膜的分辨率和伤口愈合，由于底层而容易发展疤痕和NV 遗传原因，隐形眼镜穿着或角膜移植手术，因此将防止形成 永久性疤痕和失明。