Retinal Pigmented Epithelium Reprogramming and Retina Regeneration
Retinal Pigmented Epithelium Reprogramming and Retina Regeneration
批准号:
8598851
负责人:
Katia Del Rio-Tsonis
金额:
$21.3万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2013
资助国家:
美国
项目状态:
已结题
起止时间:
2013-09-01 至 2015-08-31
关键词:
Age related macular degenerationAmericanAnimal ModelBackBioinformaticsBlindnessCell DeathCell Differentiation processCell ProliferationCellsChick EmbryoDataDegenerative DisorderDiabetic RetinopathyDiseaseElectroporationEmbryoEpithelialExcisionEyeFibroblast Growth FactorFibroblast Growth Factor 2Figs - dietaryGene Expression ProfileGenesGlaucomaHumanInjuryKnowledgeMammalsMesenchymalMessenger RNAMicroRNAsMolecularMonitorNational Eye InstituteNatural regenerationNeurogliaNeuronsOutcomePhasePigmentsPlasmidsPlayPopulationProcessProliferatingProliferative VitreoretinopathyPublishingQuantitative Reverse Transcriptase PCRRNA-Binding ProteinsRegenerative MedicineReportingRetinaRetinal DegenerationRetinal DetachmentRoleSeriesSignal TransductionSomatic CellStagingStructure of retinal pigment epitheliumTechnologyTherapeuticVisual FieldsVisual impairmentWorkZebrafishbasec-myc Genescell typeeffective therapygain of functiongenome-wideinjuredinnovationknock-downloss of functionneuroepitheliumnext generationnext generation sequencingpluripotencypublic health relevanceregenerativerepairedresearch studyresponseretinal neuronsmall moleculetissue regenerationtranscriptome sequencingtransdifferentiation
中文摘要
项目总结
英文摘要
Project Summary
Retinal degeneration leading to vision loss is the ultimate outcome of age related macular degeneration
(AMD), diabetic retinopathy and glaucoma. Current therapies offer few options to those suffering from
late stages of these diseases. In order to explore possible therapies, it is important to use animal
models with regenerative capabilities such as the chick embryo. Embryonic chicks regenerate their
retina, following retinectomy, via the process of trans-differentiation if exposed to ectopic fibroblast
growth factor 2 (FGF2). This process involves the reprogramming of the retinal pigmented epithelium
(RPE) to dedifferentiate, losing its pigment, proliferating and forming a neuroepithelium that eventually
differentiates to form all major retina cell types. For this proposal, the emphasis will be on the process
of dedifferentiation which is key to understanding how transdifferentiation works. Our preliminary data
point to a two-step dedifferentiation process where injury (retinectomy) induces the RPE to become
competent to respond to FGF2. We have identified a series of factors that are up-regulated with "injury
only" (step 1) including some pluripotency inducing factors (PiFs) and eye field transcriptional factors. In
addition, we have found that Lin-28, a PiF and a critical player in Muller glia transdifferentiation in
zebrafish, is only up-regulated upon addition of FGF2 (step 2) in the chick eye after retina removal.
Based on our preliminary data, we will investigate whether Lin-28 is required and sufficient to induce
RPE transdifferentiation in retinectomized chick eyes. We will perform gain-of-function experiments by
electroporating a plasmid containing Lin-28 and loss-of-function using morpholinos against Lin28. Our
hypothesis is that Lin-28 is sufficient to complete the RPE reprogramming process initiated by
injury signals to make new retina. The other focus of this proposal is on dissecting regulatory
components including signaling networks and mRNA-miRNA regulatory modules using an unbiased,
genome wide approach and taking advantage of state of the art technology such as Next Generation
Sequencing to perform mRNA-Seq and miRNA-Seq. We hypothesize that the two-step process
implicated in chick RPE dedifferentiation requires a unique set of regulatory molecules at each
step. This study will have a significant impact on the field of regenerative medicine since the
information obtained can be extrapolated to the process of retina repair in mammals including humans,
and specifically on the potential reprogramming of human RPE to generate new neurons. Also the
significance of identifying key miRNA molecules that could reprogram RPE is high considering
these are small molecules highly desirable for human therapeutics.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
A Roadmap to Uncover RPE Plasticity
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批准号:10639436
-
项目类别:
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资助金额:$36.13万
-
财政年份:2023
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负责人:Katia Del Rio-Tsonis
-
依托单位:
Inflammation is a driver of newt lens regeneration
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批准号:10705582
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项目类别:
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资助金额:$18.06万
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财政年份:2022
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负责人:Katia Del Rio-Tsonis
-
依托单位:
Inflammation is a driver of newt lens regeneration
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批准号:10433462
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项目类别:
-
资助金额:$21.68万
-
财政年份:2022
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负责人:Katia Del Rio-Tsonis
-
依托单位:
In vivo imaging of newt lens regeneration: Novel molecular, cellular and functional insights
-
批准号:10250409
-
项目类别:
-
资助金额:$17.52万
-
财政年份:2020
-
负责人:Katia Del Rio-Tsonis
-
依托单位:
In vivo imaging of newt lens regeneration: Novel molecular, cellular and functional insights
-
批准号:10043483
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项目类别:
-
资助金额:$20.79万
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财政年份:2020
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负责人:Katia Del Rio-Tsonis
-
依托单位:
On Determinants of Lens Regeneration
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批准号:9288485
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项目类别:
-
资助金额:$36.13万
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财政年份:2017
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负责人:Katia Del Rio-Tsonis
-
依托单位:
The role of Injury signals in RPE Reprogramming
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批准号:9902450
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项目类别:
-
资助金额:$36.13万
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财政年份:2016
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负责人:Katia Del Rio-Tsonis
-
依托单位:
The role of Injury signals in RPE Reprogramming
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批准号:9129196
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项目类别:
-
资助金额:$36.13万
-
财政年份:2016
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负责人:Katia Del Rio-Tsonis
-
依托单位:
The role of Injury signals in RPE Reprogramming
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批准号:9246537
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项目类别:
-
资助金额:$36.13万
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财政年份:2016
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负责人:Katia Del Rio-Tsonis
-
依托单位:
Retinal Pigmented Epithelium Reprogramming and Retina Regeneration
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批准号:8712501
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项目类别:
-
资助金额:$17.4万
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财政年份:2013
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负责人:Katia Del Rio-Tsonis
-
依托单位:
Signaling pathways during chick retina regeneration
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批准号:8133793
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项目类别:
-
资助金额:$26.99万
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财政年份:2007
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负责人:Katia Del Rio-Tsonis
-
依托单位:
Signaling pathways during chick retina regeneration
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批准号:7492069
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项目类别:
-
资助金额:$27.83万
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财政年份:2007
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负责人:Katia Del Rio-Tsonis
-
依托单位:
Signaling pathways during chick retina regeneration
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批准号:7313854
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项目类别:
-
资助金额:$27.48万
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财政年份:2007
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负责人:Katia Del Rio-Tsonis
-
依托单位:
Signaling pathways during chick retina regeneration
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批准号:7905714
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项目类别:
-
资助金额:$28.12万
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财政年份:2007
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负责人:Katia Del Rio-Tsonis
-
依托单位:
Signaling pathways during chick retina regeneration
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批准号:7677325
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项目类别:
-
资助金额:$28.4万
-
财政年份:2007
-
负责人:Katia Del Rio-Tsonis
-
依托单位:
Regulation of neural stem cells in retina regeneration
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批准号:6950275
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项目类别:
-
资助金额:$17.04万
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财政年份:2004
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负责人:Katia Del Rio-Tsonis
-
依托单位:
Regulation of neural stem cells in retina regeneration
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批准号:6847495
-
项目类别:
-
资助金额:$13.63万
-
财政年份:2004
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负责人:Katia Del Rio-Tsonis
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依托单位:
Molecular Pathway in Retina Regeneration
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批准号:6795333
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项目类别:
-
资助金额:$14.0万
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财政年份:2002
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负责人:Katia Del Rio-Tsonis
-
依托单位:
Molecular Pathway in Retina Regeneration
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批准号:6532125
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项目类别:
-
资助金额:$13.8万
-
财政年份:2002
-
负责人:Katia Del Rio-Tsonis
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依托单位:
Molecular Pathway in Retina Regeneration
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批准号:6641272
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项目类别:
-
资助金额:$14.0万
-
财政年份:2002
-
负责人:Katia Del Rio-Tsonis
-
依托单位:
海外基金