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：膳食补充剂 n-3 PUFA 控制角膜炎症 【摘要】：角膜作为眼睛最外层的组织,经常遭受角膜擦伤、刺伤等损伤。 导致角膜炎症的伤口、化学烧伤和热烧伤。角膜炎症也是不可或缺的 圆锥角膜、长期佩戴隐形眼镜、角膜移植手术等遗传性疾病。 炎症失衡和伤口愈合不当（消退）会导致角膜疤痕和 新生血管形成（NV）会导致失明。全球失明病例中多达四分之一是 归因于疤痕或纤维化产生的角膜混浊，代表着巨大的经济和社会损失 负担。角膜纤维化发展的主要原因是由于以下原因导致的伤口愈合过程缺陷 炎症及其消退的不平衡。目前，尚无 FDA 批准的药物可以促进适当的治疗 角膜伤口愈合。我们假设鱼油膳食中的 n-3 多不饱和脂肪酸 (PUFA) 补充剂将通过减少慢性炎症和增强角膜纤维化来抑制角膜纤维化和 NV 解决和伤口愈合。 在炎症和组织愈合过程中，N-3 PUFA（如二十碳五烯酸、EPA 和 二十二碳六烯酸 (DHA)，可产生多种生物活性脂质介质（如分解素、神经保护素） 和maresins）在炎症消退和组织愈合中发挥重要作用。虽然实质性 现有研究数据表明 n-3 PUFA（DHA 和 EPA）对许多人体系统的益处 疾病中，n-3 PUFA 在角膜愈合和视力恢复中的作用尚未得到研究。我们建议 确定 OmegaRx2 鱼油中 n-3 PUFA 膳食补充剂的功效（Zone Labs） 预防角膜损伤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 人类增强膳食补充剂，帮助平衡炎症和 提高角膜的分辨率和伤口愈合能力，这些角膜由于潜在的原因而容易产生疤痕和 NV 遗传原因、佩戴隐形眼镜或角膜移植手术，从而防止形成 永久性疤痕和失明。