Role in Myopia Development of Retinal Pigment Epithelium - A New Therapeutic Targ
视网膜色素上皮在近视发展中的作用——一种新的治疗目标
基本信息
- 批准号:8568409
- 负责人:
- 金额:$ 14.97万
- 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
- 起止时间:2013-09-30 至 2018-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcademiaAffectAnimal ModelAnimalsApicalApomorphineAwardBloodBone Morphogenetic Protein GeneBone Morphogenetic ProteinsCaliforniaCell Culture TechniquesCell Differentiation processCellsCellular biologyChoroidClinicalCloningCommunitiesDataDevelopmentDevelopmental BiologyDisciplineDiseaseDoctor of PhilosophyDopamineDopamine AgonistsElectrophysiology (science)ElectroporationElectroretinographyEmbryonic DevelopmentEnvironmentEnzyme-Linked Immunosorbent AssayExtracellular MatrixEyeEye diseasesFamilyFrequenciesFundingGene ExpressionGenesGoalsGrantGrowthGrowth FactorHarvestHumanImageImmunohistochemistryIn VitroIndividualInvestigationJournalsK-Series Research Career ProgramsKnowledgeMeasurementMeasuresMediatingMedicineMentorsMentorshipModelingMolecular BiologyMorphogenesisMyopiaOphthalmologyOptic NerveOptical Coherence TomographyOpticsOutcomePaperPhysiologyPlayPopulationPositioning AttributePreparationPrevalenceProductionProductivityProtein FamilyProtein SecretionPublicationsRefractive ErrorsRegulationResearchResearch PersonnelResearch ProposalsRetinaRetinalRiskRoleSan FranciscoScanningScientistSenior ScientistSeveritiesSignal TransductionStructure of retinal pigment epitheliumTechniquesTechnologyTestingTherapeutic InterventionTherapeutic StudiesTimeTissuesTrainingTranslational ResearchUltrasonographyUnited States National Institutes of HealthUniversitiesVirusWestern Blottingage groupbonebone morphogenetic protein 2careercareer developmenteconomic implicationexperiencefetalfollow-upgene therapyimmunocytochemistryin vitro Modelin vivoknock-downlensmembernew therapeutic targetnovelnovel therapeuticspreventprofessorprogramsprotein expressionpublic health relevancereceptorresearch studyresponseskillssocial implicationsubretinal injectionvision science
项目摘要
Zhang Y. Role in Myopia Development of Retinal Pigment Epithelium - A New Therapeutic Target ?
Project Summary
The Mentored Clinical Scientist Research Career Development Award (K08) candidate, Yan Zhang, earned her
clinical degrees in Medicine and Ophthalmology, and she is currently pursuing her Ph.D. degree in the Vision
Science Program at University of California, Berkeley, which will be completed in the Spring 2013. She has
already one publication in a high profile journal from the latter research, with 2 more papers soon to be
submitted, demonstrating both good productivity and research drive. As the next step towards a career as an
independent clinician scientist in academia, Dr. Zhang is applying for a K08 career award to obtain advanced
training - to further expand her scientific knowledge and biomedical technical skills through investigations
into the roles of retinal pigment epithelium (RPE) and bone morphogenetic proteins (BMPs) in eye growth
regulation and myopia development, with the RPE targeted in related exploratory studies of gene therapy for
myopia treatment. Over the course of her studies to-date, Dr. Zhang has received broad training in many of
the disciplines required for successfully executing her proposed project. She proposed to cover remaining
deficiencies with additional coursework and hands-on training during the 5-year training period of the K
award for which she is applying. Thus at the end of this 5-year career development award Dr. Zhang should
be well prepared for a career as an independent researcher, successfully competing for research funds. The
proposed study will be conducted primarily under the mentorship of Dr. Christine Wildsoet, who is a well-
known leading scientist in the field of myopia and eye growth regulation. Myopia, or nearsightedness, is one
of most common refractive errors in humans and significantly contributes to the global burden of eye disease.
It is the product of eyes growing excessively long. The prevalence and the severity of myopia have risen
worldwide during the past several decades, stimulating increased research into the underlying mechanisms,
an essential step in developing effective anti-myopia therapies. Previous studies have suggested that early eye
growth regulation is largely localized to eye itself. The RPE is known to be a component of the blood-retina
barrier, with critical roles in maintaining normal retinal and choroidal functions. Recent research findings,
mostly from the Wildsoet lab and much of it belongs to Dr. Zhang, suggest that it also plays an essential role in
the regulation of eye growth. The proposal focuses on the role of RPE in myopia development and as a
potential target for myopia therapy, with 3 specific aims: (1) to investigate the role of RPE-derived bone
morphogenetic proteins (BMPs) in eye growth regulation; (2) to investigate the effects of dopamine (DA) on
RPE-BMP expression and secretion; (3) to investigate over-expression of BMPs in RPE as a potential gene
therapy for myopia. Complementary experiments include in vivo animal studies, using the chick as an myopia
model, and in vitro cell culture studies, using human fetal (hf) RPE as a model, exploiting Dr. Zhang's
experience with both models. In vivo structural and functional measurements will use advanced technologies,
including high frequency A-scan ultrasonography, spectral domain optical coherence tomography (SD-OCT)
and electroretinography (ERG). A variety of molecular and cell biology techniques will also be used including
cloning, real-time PCR, Western blot, ELISA, and immunohistochemistry. Techniques most commonly
encountered in ocular gene therapy research, including electroporation and subretinal injection, will also be
employed. The proposed research will be conducted under the co-mentorship of Dr. Jeanette Hyer from UC
San Francisco, who is an expert in developmental biology, with a focus on chick embryogenesis. Three senior
scientists have also agreed to serve as consultants on her project: Professor Lawrence Rizzolo (Yale University)
and Dr. Sheldon Miller (NEI/NIH), who are experts in RPE physiology and electrophysiology, and Professor
Kunxin Luo (UC Berkeley), whose research focus is the TGF-¿ family including BMPs and their roles in cell
differentiation, tissue morphogenesis, and extracellular matrix production. UC Berkeley and UC San Francisco
offer world-class research environments and support for the preparation and training of young scientists for
independent research careers.
张颖。视网膜色素上皮在近视发展中的作用-一个新的治疗靶点?
项目成果
期刊论文数量(0)
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Yan Zhang其他文献
Yan Zhang的其他文献
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{{ truncateString('Yan Zhang', 18)}}的其他基金
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