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Dietary Supplement of n-3 PUFA to Control Corneal Inflammation

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
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-07-01 至 2024-05-31
关键词:
3-DimensionalAreaBlindnessBurn injuryCeramidesChemicalsChronicCicatrixComplexContact LensesCorneaCorneal AbrasionCorneal DiseasesCorneal InjuryCorneal NeovascularizationCorneal OpacityCorneal dystrophyDataDevelopmentDietDietary SupplementationDocosahexaenoic AcidsDue ProcessEconomicsEicosapentaenoic AcidEquilibriumExtracellular MatrixEyeFDA approvedFeedbackFibroblastsFibrosisFish OilsG-Protein-Coupled ReceptorsGTP-Binding Protein alpha Subunits, GsGeneticGenetic DiseasesGenetic TranscriptionHumanInfectionInflammationInvestigationKeratoconusKeratoplastyKnock-outMediator of activation proteinMetabolismMusMyofibroblastN-3 polyunsaturated fatty acidOperative Surgical ProceduresOralOutcomePathologicPathway interactionsPatientsPharmaceutical PreparationsPhenotypePlayProcessProtein IsoformsPuncture woundResearchResolutionRoleSPHK1 enzymeSignal PathwaySignal TransductionSiteSphingolipidsSphingosineSphingosine-1-Phosphate ReceptorStromal CellsSystemic diseaseTestingTherapeuticTissuesTranscriptional ActivationTransforming Growth Factor beta ReceptorsTransforming Growth FactorsTranslatingTransplantation SurgeryTraumaUnited States National Institutes of HealthUp-RegulationWild Type Mousecorneal epithelial wound healingcorneal regenerationcorneal scardietary supplementseffective therapyfibrogenesishealinghuman diseaseimprovedin vitro Modelin vivoinhibitor/antagonistlipid mediatormigrationmouse modelneovascularizationnew therapeutic targetnovelparent grantpreventreceptorresponsesight restorationsmall molecule inhibitorsphingosine 1-phosphatetherapeutic developmentwound healing

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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.
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Sphingolipids and their Impact in Corneal Wound Healing
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