Mechanism of intravitreal VEGF-A165a and topical calcitriol for the treatment of retinopathy of prematurity
玻璃体内注射VEGF-A165a联合局部骨化三醇治疗早产儿视网膜病变的机制
基本信息
- 批准号:10645643
- 负责人:
- 金额:$ 23.61万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-30 至 2026-08-31
- 项目状态:未结题
- 来源:
- 关键词:AdultAffectAgeAirAngiogenic ProteinsApoptosisAppointmentBindingBiochemistryBiologicalBiometryBlindnessBlood VesselsBlood capillariesCalcitriolCataractChildhoodDiabetes MellitusDiseaseDoseElectroretinographyEndothelial Growth Factors ReceptorEnvironmentEquilibriumExtramural ActivitiesEye diseasesEyedropsFluorescein AngiographyGenesGoalsGrowthGrowth FactorHalf-LifeHistologicHistopathologyHumanHyperoxiaKnowledgeLaboratoriesLeadLongitudinal StudiesLow-Level Laser TherapyMalignant NeoplasmsMeasuresMediatingMentorsMethodsMolecularMolecular GeneticsMonoclonal AntibodiesMusOphthalmologyOptical Coherence TomographyOptometristOxygenPathogenesisPathway interactionsPatientsPediatricsPharmaceutical PreparationsPharmacotherapyPhasePhase TransitionPhenotypePremature InfantProtein IsoformsProtein KinaseProteinsRNA SplicingRefractive ErrorsRegulationResearchResearch EthicsResearch PersonnelResourcesRetinaRetinal DetachmentRetinal DiseasesRetinopathy of PrematurityRoleSignal TransductionSignaling ProteinStructureSynapsesTechniquesTestingTherapeuticThickToxic effectTrainingTranslational ResearchUnited StatesUnited States National Institutes of HealthUniversitiesVEGFA geneVariantVascular Endothelial Growth FactorsVascularizationVeinsVenousVisionVisualVisual FieldsVitamin DVulnerable PopulationsWisconsinangiogenesisarterial tortuositybevacizumabcareercentral retinal arteryclinical translationeffective therapyexperienceglial activationhistological studiesimprovedin vivoinnovationintraperitonealintravitreal injectionmouse modelneovascularizationnovelnovel therapeuticsoverexpressionpostnatalpreservationprofessorprotein expressionresearch studyretina blood vessel structureretinal angiogenesisskillssuccesssynaptogenesissystemic toxicitytherapeutically effectivetrend
项目摘要
PROJECT SUMMARY
Dr. Olachi Mezu-Ndubuisi is a neonatologist with a background training as an optometrist, now an Assistant
Professor of Pediatrics with an affiliate appointment in the Department of Ophthalmology at University of
Wisconsin (UW). She combines these experiences in her research studying Retinopathy of Prematurity (ROP).
ROP is a bi-phasic disease of abnormal retinal vascularization in premature infants, characterized by
dysregulation of vascular endothelial growth factor (VEGF). ROP has no cure, and existing therapies have
adverse systemic effects and long-term deficits. Dr. Mezu-Ndubuisi developed a non-invasive method of
visualizing retinal blood vessels in a mouse model of oxygen-induced retinopathy (OIR) using fluorescein
angiography. She correlated in vivo retinal vascular changes (arterial tortuosity, venous dilation, and capillary
vascularity) to structure and function, and performed histological studies to show unique long-term features of
OIR mice, such as prolonged cellular apoptosis, glial activation, and ectopic formation of synapses. Having
defined the in vivo and histologic OIR phenotypes, she seeks to use molecular techniques to enhance
understanding of VEGF regulation in ROP in order to develop safe and effective therapies. In her preliminary
studies, there was a 6-fold increase in total mouse Vegfa164 levels at post-natal day (P) 13, early in Phase 2
ROP, in OIR mice compared to RA mice, and Vegfa164b showed a 1.3-fold higher trend in OIR than RA mice at
P10 (peak of retinal vaso-obliteration during hyperoxia). This suggests that an imbalance of VEGF isoforms
occurs in ROP. She then administered the pro-angiogenic isoform of VEGF-A165, VEGF-A165a, in sustained
release microparticles which resulted in earlier retinal revascularization with improved arterial tortuosity and vein
dilation. She next compared topical calcitriol (active form of vitamin D) eyedrop to intraperitoneal (IP) calcitriol
and both inhibited retinal angiogenesis later in Phase 2 ROP, but topical calcitriol did not cause growth restriction
like IP calcitriol. Dr. Mezu-Ndubuisi hypothesizes that using intravitreal VEGF-A165a early in Phase 2 and topical
calcitriol later in Phase 2, would rescue the abnormal OIR in vivo and histologic phenotypes. In this K08, Dr.
Mezu-Ndubuisi will determine the most effective and least toxic dose of intravitreal VEGF microparticles or free
intravitreal VEGF protein and topical calcitriol in Phase 2 ROP (Aim 1), and then study the molecular mechanisms
by which VEGF-A165a and calcitriol regulate angiogenic signaling in ROP (Aim 2). UW provides an excellent
academic environment, state-of-the-art facilities, and academic resources dedicated to Dr. Mezu-Ndubuisi’s
success. She has strong intra-mural and extra-mural mentoring from well-established NIH investigators and
experts in ROP, molecular genetics, angiogenesis, and Vitamin D. Dr. Mezu-Ndubuisi’s career goals and
objectives include a detailed training plan to increase her knowledge in biostatistics, biochemistry,
histopathology, molecular signaling, and research ethics and laboratory skills. This will enable her successful
transition to research independence and clinical translation of her research.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Olachi Joy Mezu-Ndubuisi其他文献
Olachi Joy Mezu-Ndubuisi的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Olachi Joy Mezu-Ndubuisi', 18)}}的其他基金
Mechanism of intravitreal VEGF-A165a and topical calcitriol for the treatment of retinopathy of prematurity
玻璃体内注射VEGF-A165a联合局部骨化三醇治疗早产儿视网膜病变的机制
- 批准号:
10688094 - 财政年份:2021
- 资助金额:
$ 23.61万 - 项目类别:
相似海外基金
Hormone therapy, age of menopause, previous parity, and APOE genotype affect cognition in aging humans.
激素治疗、绝经年龄、既往产次和 APOE 基因型会影响老年人的认知。
- 批准号:
495182 - 财政年份:2023
- 资助金额:
$ 23.61万 - 项目类别:
Investigating how alternative splicing processes affect cartilage biology from development to old age
研究选择性剪接过程如何影响从发育到老年的软骨生物学
- 批准号:
2601817 - 财政年份:2021
- 资助金额:
$ 23.61万 - 项目类别:
Studentship
RAPID: Coronavirus Risk Communication: How Age and Communication Format Affect Risk Perception and Behaviors
RAPID:冠状病毒风险沟通:年龄和沟通方式如何影响风险认知和行为
- 批准号:
2029039 - 财政年份:2020
- 资助金额:
$ 23.61万 - 项目类别:
Standard Grant
Neighborhood and Parent Variables Affect Low-Income Preschool Age Child Physical Activity
社区和家长变量影响低收入学龄前儿童的身体活动
- 批准号:
9888417 - 财政年份:2019
- 资助金额:
$ 23.61万 - 项目类别:
The affect of Age related hearing loss for cognitive function
年龄相关性听力损失对认知功能的影响
- 批准号:
17K11318 - 财政年份:2017
- 资助金额:
$ 23.61万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
9320090 - 财政年份:2017
- 资助金额:
$ 23.61万 - 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
10166936 - 财政年份:2017
- 资助金额:
$ 23.61万 - 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
9761593 - 财政年份:2017
- 资助金额:
$ 23.61万 - 项目类别:
How age dependent molecular changes in T follicular helper cells affect their function
滤泡辅助 T 细胞的年龄依赖性分子变化如何影响其功能
- 批准号:
BB/M50306X/1 - 财政年份:2014
- 资助金额:
$ 23.61万 - 项目类别:
Training Grant
Inflamm-aging: What do we know about the effect of inflammation on HIV treatment and disease as we age, and how does this affect our search for a Cure?
炎症衰老:随着年龄的增长,我们对炎症对艾滋病毒治疗和疾病的影响了解多少?这对我们寻找治愈方法有何影响?
- 批准号:
288272 - 财政年份:2013
- 资助金额:
$ 23.61万 - 项目类别:
Miscellaneous Programs














{{item.name}}会员




