Role of the nerve regeneration-associated gene Sox11 in promoting corneal innervation and epithelial cell repair in dry eye
神经再生相关基因Sox11在促进干眼角膜神经支配和上皮细胞修复中的作用
基本信息
- 批准号:9767195
- 负责人:
- 金额:$ 35.6万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-09-01 至 2021-08-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAfferent NeuronsAnimalsApoptosisAttenuatedBehaviorCaliberCell ProliferationCellsControl AnimalCorneaDataDefectDependovirusDevelopmentEmbryoEmbryonic DevelopmentEnterobacteria phage P1 Cre recombinaseEpithelial Cell ProliferationEpithelial CellsEpitheliumExcisionEyeEye diseasesFeelingFiberFilmFluoresceinGene ExpressionGene TargetingGenesHealthHistologyHypesthesiaImmunohistochemistryIn Situ Nick-End LabelingKnock-outKnockout MiceLacrimal gland structureLeadMechanicsMediatingMorphologyMusNatural regenerationNerveNerve RegenerationNeuronsOphthalmologistOptometristPainPathologicPathologyPatientsPeripheral nerve injuryPlayPopulationProcessProteinsResearchReverse Transcriptase Polymerase Chain ReactionRoleSOX11 geneSalineSensorySensory ThresholdsSpinal GangliaStainsStimulusStructure of trigeminal ganglionSurfaceSymptomsSystemTissuesTransgenic MiceTrigeminal SystemTubulinUnited StatesUp-RegulationViral VectorVisionVisitactivating transcription factor 3axon growthcell injurycorneal epitheliumeye drynesshealingimprovedin vivoinsightknockout animalmature animalnerve injurynerve supplynovelnovel therapeuticsocular painoverexpressionpreventprogramsrelease factorrepairedresponseresponse to injurysham surgerytranscription factor
项目摘要
Dry eye disease results from an inadequate tear film on the corneal surface that can result in ocular pain and in
some cases serious vision problems. Symptoms of dry eye disease are a primary reason for patient visits to
ophthalmologists and optometrists in the United States, and for many sufferers treatment remains inadequate.
Previous studies demonstrate a clear role for corneal primary afferent neurons in maintaining the corneal
epithelium under normal conditions, presumably through the release of factors that prevent epithelial cell
apoptosis and stimulate proliferation. However, the role of these sensory neurons in supporting corneal healing
under pathological conditions such as dry eye remains unknown. We hypothesize that dry eye disease and its
associated corneal damage initiates an injury-response program in corneal afferent neurons that involves the
upregulation of nerve regeneration-associated genes, such as the transcription factor Sox11, in the trigeminal
ganglion. It is proposed that upregulation of Sox11 in dry eye is critical for maintaining corneal afferent
innervation and thus maintaining the trophic support required to promote corneal healing. The aims in this
proposal explore the impact of Sox11 expression in the trigeminal ganglion and the role it plays in maintaining
corneal afferent innervation and promoting corneal healing in dry eye. Aim 1 will examine the expression of
Sox11 and its downstream gene targets in corneal afferent cell bodies of the trigeminal ganglion following
induction of dry eye by lacrimal gland excision. Aim 2 will determine the role of Sox11 in maintaining corneal
innervation and sensitivity in dry eye, utilizing a transgenic mouse line in which Sox11 is deleted only in small
diameter sensory fibers (including corneal primary afferent neurons). The contribution of Sox11 in these
neurons to corneal nerve morphology and functional sensitivity will be examined following lacrimal gland
excision. Using these same mice, Aim 3 will determine how deletion of Sox11 in corneal primary afferent
neurons impacts the condition of the corneal epithelium following lacrimal gland excision. Corneal fluorescein
staining and epithelial cell proliferation and apoptosis will be examined. Finally, Aim 4 will utilize a viral vector
to drive the overexpression Sox11 in small diameter sensory fibers, including the corneal afferent neurons, to
determine if increasing expression of Sox11 in these neurons can further promote or improve corneal healing
under dry eye conditions. The proposed studies will elucidate novel mechanisms that, if targeted appropriately,
could simultaneously maintain corneal innervation and facilitate corneal healing in patients suffering from dry
eye disease.
干眼症是由于角膜表面的泪膜不充分而引起的,可导致眼睛疼痛和疼痛
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
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IAN D MENG其他文献
IAN D MENG的其他文献
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{{ truncateString('IAN D MENG', 18)}}的其他基金
Interdisciplinary Center of Excellence for the Study of Pain and Sensory Function
疼痛和感觉功能研究跨学科卓越中心
- 批准号:
10414545 - 财政年份:2022
- 资助金额:
$ 35.6万 - 项目类别:
Interdisciplinary Center of Excellence for the Study of Pain and Sensory Function
疼痛和感觉功能研究跨学科卓越中心
- 批准号:
10631127 - 财政年份:2022
- 资助金额:
$ 35.6万 - 项目类别:
Interdisciplinary Center of Excellence for the Study of Pain and Sensory Function
疼痛和感觉功能研究跨学科卓越中心
- 批准号:
10176516 - 财政年份:2012
- 资助金额:
$ 35.6万 - 项目类别:
Interdisciplinary center of excellence for the study of pain and sensory function
疼痛和感觉功能研究跨学科卓越中心
- 批准号:
8529574 - 财政年份:2012
- 资助金额:
$ 35.6万 - 项目类别:
Interdisciplinary center of excellence for the study of pain and sensory function
疼痛和感觉功能研究跨学科卓越中心
- 批准号:
8216804 - 财政年份:2012
- 资助金额:
$ 35.6万 - 项目类别:
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