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：饮食补充n-3 PUFA控制角膜炎症 翻译后摘要：角膜是最外层的组织在眼睛遭受定期损伤角膜擦伤，穿刺 伤口，化学和热烧伤，诱发角膜炎症。角膜炎症也是 遗传性疾病，如圆锥角膜、长期戴隐形眼镜和手术角膜移植。 炎症的不平衡和不适当的伤口愈合（解决）会导致角膜瘢痕， 新生血管形成（NV）导致失明。全世界多达四分之一的失明病例是 归因于瘢痕形成或纤维化产生的角膜混浊，代表了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有缺陷的伤口愈合过程： 炎症及其解决的不平衡。目前，没有FDA批准的药物， 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） 补充将通过减少慢性炎症和增强角膜内皮细胞的增殖来抑制角膜纤维化和NV。 解决和伤口愈合。 在炎症和组织愈合期间，它是N-3 PUFA（如二十碳五烯酸、EPA和EPA）。 二十二碳六烯酸，DHA），其产生几种生物活性脂质介质（如消退素、神经保护素 和maresins），其在炎症消退和组织愈合中起重要作用。虽然数量可观， 关于n-3 PUFA（DHA和EPA）在许多人体系统中的益处的研究数据是可用的。 在角膜疾病中，尚未研究n-3 PUFA在角膜愈合和视力恢复中的作用。我们提出 确定来自OmegaRx 2鱼油的n-3 PUFA的饮食补充的功效（Zone Labs） 预防小鼠角膜损伤模型中的角膜瘢痕和NV。我们预计我们的研究最终将 转化为n-3 PUFA的人类增强膳食补充剂，以帮助平衡炎症， 改善角膜的分辨率和伤口愈合，由于潜在的 遗传原因，隐形透镜佩戴或角膜移植手术，从而将防止形成眼镜 永久性疤痕和失明。