Preservation of Limbal Stem Cell Function in Corneal Injury
角膜损伤后角膜缘干细胞功能的保存
基本信息
- 批准号:10457936
- 负责人:
- 金额:$ 39.77万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-01 至 2024-01-31
- 项目状态:已结题
- 来源:
- 关键词:AblationAcuteAnimal ModelAqueous HumorBindingBiochemicalBiological ProcessBlindnessBlood CirculationBlood VesselsBurn injuryCardiovascular DiseasesCell LineageCell membraneChemistryChronicCicatrixClustered Regularly Interspaced Short Palindromic RepeatsComplexCorneaCorneal DiseasesCorneal InjuryDevelopmentDiseaseDoseEngineeringEpithelialEpithelial CellsExhibitsFibroblastsFibrosisFilmFormulationGenesGeneticGoblet CellsHealthHealth PromotionHomeostasisHumanImaging DeviceInfiltrationInjuryIntegumentary systemLongevityMediatingMembraneModelingMolecularMusMuscleMutagenesisMyofibroblastMyopathyNatural regenerationOcular PhysiologyOperative Surgical ProceduresOryctolagus cuniculusOutcomeOutcomes ResearchPathologicPathologyPersonsPharmacologyPhysiologicalPreventionProcessProductionProtein FamilyProteinsProtocols documentationRattusRecombinantsRegenerative capacityResearchRoleSafetySerumSignal TransductionStressTRIM FamilyTechniquesTestingThinnessTissuesTopical applicationTransforming Growth Factor betaTraumaVascularizationalkalinityangiogenesisbiochemical toolscell injurycombatcorneal epithelial wound healingcorneal epitheliumcorneal regenerationcorneal repaircorneal scareffective therapyepithelium regenerationexperimental studyextracellulargene repairhealingimprovedimproved outcomein vivoinjury and repairlimballive cell imagingmigrationmouse modelnovelnovel therapeuticsoxidative damagepreservationregenerative tissuerepairedresponsescale upstemstem cell functionstem cell nichestem cell proliferationstem cellssynergismtissue injurytissue regenerationtissue repairtranslational applicationswoundwound healing
项目摘要
Project Summary
Corneal wound healing is a complex and coordinated process involving injury repair to the epithelial layer
and stimulation of limbal stem cell (LSC) proliferation for tissue regeneration. Prevention of excessive
stromal myofibroblast activation and vascular ingrowth is also imperative to avoid fibrosis and angiogenesis,
which can compromise transparency of the cornea. An approach that can functionally target multiple steps
in corneal wound healing may have the potential to significantly improve healing outcomes, leading to novel
therapeutic options. This project stems from our novel findings that reveal a vital role for MG53, a tissue repair
gene, in modulating LSC function associated with corneal injury-repair. We show that genetic ablation of MG53
leads to injury-induced corneal epithelial thinning, conjunctivalization, stromal fibrosis, and vascularization, all
hallmarks of limbal stem cell deficiency (LSCD). Mice with sustained elevation of MG53 in circulation show
increased tissue regenerative capacity with enhanced LSC function. MG53 is present in the human tear film,
aqueous humor, and corneal epithelial cells, supporting its potential function in corneal homeostasis and
wound healing. Using in vivo corneal injury models, we find that MG53 promotes corneal transparency by
facilitating epithelial viability and reducing post-injury fibrosis and vascularization. Experiments outlined in this
project are centered on testing the hypothesis that MG53 constitutes an active component of the corneal injury-
repair and regeneration by maintaining the health of LSCs, as well as controlling the fibrotic response of
stromal fibroblasts. We envision that pharmacological formulation to enhance the synergy between MG53
delivery, LSC function, and fibrotic control could be a potentially effective means to treat corneal diseases. The
outcome of this research shall have significant translational value in developing potentially effective therapies
to treat corneal injury and fibrosis associated with corneal disease.
项目总结
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Serp-1 Promotes Corneal Wound Healing by Facilitating Re-epithelialization and Inhibiting Fibrosis and Angiogenesis.
- DOI:10.3389/fcvm.2021.649124
- 发表时间:2021
- 期刊:
- 影响因子:3.6
- 作者:Ju B;Guo O;Benissan-Messan DZ;Shawver MH;Chen P;Geng B;Wei S;Yaron JR;Lucas AR;Zhu H
- 通讯作者:Zhu H
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Heather Chandler其他文献
Heather Chandler的其他文献
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{{ truncateString('Heather Chandler', 18)}}的其他基金
Inhibiting neovascularization for corneal wound healing
抑制新生血管形成促进角膜伤口愈合
- 批准号:
10366187 - 财政年份:2022
- 资助金额:
$ 39.77万 - 项目类别:
Inhibiting neovascularization for corneal wound healing
抑制新生血管形成促进角膜伤口愈合
- 批准号:
10557867 - 财政年份:2022
- 资助金额:
$ 39.77万 - 项目类别:
First Aid Medicine to Treat Vesicant Induced Corneal Injury
治疗疱疹引起的角膜损伤的急救药物
- 批准号:
10487854 - 财政年份:2022
- 资助金额:
$ 39.77万 - 项目类别:
First Aid Medicine to Treat Vesicant Induced Corneal Injury
治疗疱疹引起的角膜损伤的急救药物
- 批准号:
10707316 - 财政年份:2022
- 资助金额:
$ 39.77万 - 项目类别:
Preservation of Limbal Stem Cell Function in Corneal Injury
角膜损伤后角膜缘干细胞功能的保存
- 批准号:
9803337 - 财政年份:2019
- 资助金额:
$ 39.77万 - 项目类别:
Preservation of Limbal Stem Cell Function in Corneal Injury
角膜损伤后角膜缘干细胞功能的保存
- 批准号:
10224209 - 财政年份:2019
- 资助金额:
$ 39.77万 - 项目类别:
Preservation of Limbal Stem Cell Function in Corneal Injury
角膜损伤后角膜缘干细胞功能的保存
- 批准号:
10002286 - 财政年份:2019
- 资助金额:
$ 39.77万 - 项目类别:
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