Novel mechanism controlling calcium signaling to treat and prevent neurodegeneration in early stage glaucoma
控制钙信号传导以治疗和预防早期青光眼神经变性的新机制
基本信息
- 批准号:10333217
- 负责人:
- 金额:$ 37.59万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-02-01 至 2024-01-31
- 项目状态:已结题
- 来源:
- 关键词:Acquired Immunodeficiency SyndromeAcuteAffectAgingAnimal ModelAttenuatedBiologicalBiological ModelsBiomimeticsBlindnessCalcium ChannelCalcium SignalingChronicClinicalClinical ManagementClinical TrialsCombined Modality TherapyComplementComplexDataDefense MechanismsDegenerative DisorderDevelopmentDiseaseDominant-Negative MutationDrug TargetingEye diseasesGlaucomaGoalsHealthHealthcareHeart DiseasesHomeostasisHomer 1Homer 1aImmediate-Early GenesIn VitroInterventionMalignant NeoplasmsMeasuresMinorityModelingMolecularNatureNerve DegenerationNeuronsNeuroprotective AgentsOperative Surgical ProceduresOphthalmologyOptic NervePathogenesisPathologicPatientsPerformancePharmacologic SubstancePharmacotherapyPhysiologic Intraocular PressurePhysiologicalPlant RootsPopulationPre-Clinical ModelProcessProtein IsoformsProteinsPublishingResearchRetinaRetinal Ganglion CellsSecond Messenger SystemsSeverity of illnessSignal TransductionStrategic PlanningSynaptic TransmissionTargeted ResearchTestingTherapeuticTimeTreatment EfficacyUnited StatesVisionVision researchVisualVisual impairmentbasecostdesignexpectationexperimental studyfunctional restorationgene producthealth care deliveryhealth disparityhuman diseaseimprovedin vivoineffective therapiesnerve damageneuroprotectionnormal agingnovelnovel therapeutic interventionpre-clinicalpreservationpreventresponserestorationretinal damageretinal neuronside effecttargeted treatmenttherapeutic targettherapy designtherapy outcometreatment strategyvisual performance
项目摘要
Project Summary/Abstract
The proposal is in response to NEI's strategic plan, described recently by NEI in “Vision Research:
Needs, Gaps, and Opportunities”, and focuses on our most recent discoveries of a novel neuronal
mechanism rooted at the intersection of aging and the biological mechanisms of eye disease identified
as a high programmatic priority. The proposed research targets a novel mechanism of neuroprotection
utilizing intracellular calcium channels as drug targets to treat neurodegeneration in glaucoma.
Specifically, we plan to determine mechanisms of action and to measure preservation of neuronal
viability and function in model systems of glaucoma. The proposed research will allow us to generate
preclinical data needed for the development of novel neuroprotectants to complement existing therapies
targeting intraocular pressure: The intracellular free Ca2+ concentration of retinal ganglion cells like in
other neurons of the CNS is highly regulated and subject to dysregulation during aging. For the
development of acute and chronic degenerative diseases including glaucoma reducing the viability and
function of retinal ganglion cells (RGCs) several studies indicate that both changes in intracellular second
messenger concentration and pathological increases in the intracellular Ca2+ concentration promote
pathogenesis. The present application will test the hypothesis that Ca2+ signaling of RGCs is functionally
regulated by an immediate early gene product upregulated in RGCs after a neurodegenerative insult to
generate a cellular defense mechanism. This hypothesis is based on strong preliminary evidence that
normal aging of the retina is mechanistically similar to glaucoma disease processes and can be exploited
to devise novel treatments for glaucoma. The proposed experiments designed to test this hypothesis will
investigate the molecular, cellular and functional mechanisms underlying this interaction under
experimentally induced disease conditions in models of glaucoma. The overall goal of the proposed
study is to identify a novel mechanism of RGC neuroprotection and determine its potential as a strategy
for neuroprotective therapies targeting RGCs. This therapy approach will have the potential to be both
preventative and therapeutic in nature and to complement existing treatment designs and rationales.
项目总结/文摘
项目成果
期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Cannabinoids and endocannabinoids as therapeutics for nervous system disorders: preclinical models and clinical studies.
- DOI:10.4103/1673-5374.382220
- 发表时间:2024-04
- 期刊:
- 影响因子:6.1
- 作者:Duncan RS;Riordan SM;Gernon MC;Koulen P
- 通讯作者:Koulen P
Novel Machine-Learning Based Framework Using Electroretinography Data for the Detection of Early-Stage Glaucoma.
- DOI:10.3389/fnins.2022.869137
- 发表时间:2022
- 期刊:
- 影响因子:4.3
- 作者:Gajendran, Mohan Kumar;Rohowetz, Landon J.;Koulen, Peter;Mehdizadeh, Amirfarhang
- 通讯作者:Mehdizadeh, Amirfarhang
Analysis of Glaucoma Associated Genes in Response to Inflammation, an Examination of a Public Data Set Derived from Peripheral Blood from Patients with Hepatitis C.
- DOI:10.2147/opth.s364739
- 发表时间:2022
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
N-acylethanolamide metabolizing enzymes are upregulated in human neural progenitor-derived neurons exposed to sub-lethal oxidative stress.
- DOI:10.3389/fncel.2022.902278
- 发表时间:2022
- 期刊:
- 影响因子:5.3
- 作者:Duncan, R. Scott;Riordan, Sean M.;Hall, Conner W.;Payne, Andrew J.;Chapman, Kent D.;Koulen, Peter
- 通讯作者:Koulen, Peter
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Peter Koulen其他文献
Peter Koulen的其他文献
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{{ truncateString('Peter Koulen', 18)}}的其他基金
Novel mechanism controlling calcium signaling to treat and prevent neurodegeneration in early stage glaucoma
控制钙信号传导以治疗和预防早期青光眼神经变性的新机制
- 批准号:
10288383 - 财政年份:2020
- 资助金额:
$ 37.59万 - 项目类别:
Novel mechanism controlling calcium signaling to treat and prevent neurodegeneration in early stage glaucoma
控制钙信号传导以治疗和预防早期青光眼神经变性的新机制
- 批准号:
9916194 - 财政年份:2020
- 资助金额:
$ 37.59万 - 项目类别:
Novel mechanism controlling calcium signaling to treat and prevent neurodegeneration in early stage glaucoma
控制钙信号传导以治疗和预防早期青光眼神经变性的新机制
- 批准号:
10190022 - 财政年份:2020
- 资助金额:
$ 37.59万 - 项目类别:
Novel mechanism controlling calcium signaling to treat and prevent neurodegeneration in early stage glaucoma
控制钙信号传导以治疗和预防早期青光眼神经变性的新机制
- 批准号:
10087941 - 财政年份:2020
- 资助金额:
$ 37.59万 - 项目类别:
Novel pro-drug pharmacotherapy to prevent neuronal and cell degeneration in AMD
预防 AMD 神经元和细胞变性的新型前药药物疗法
- 批准号:
10216112 - 财政年份:2019
- 资助金额:
$ 37.59万 - 项目类别:
Novel pro-drug pharmacotherapy to prevent neuronal and cell degeneration in AMD
预防 AMD 神经元和细胞变性的新型前药药物疗法
- 批准号:
10213749 - 财政年份:2019
- 资助金额:
$ 37.59万 - 项目类别:
Novel pro-drug pharmacotherapy to prevent neuronal and cell degeneration in AMD
预防 AMD 神经元和细胞变性的新型前药药物疗法
- 批准号:
10018027 - 财政年份:2019
- 资助金额:
$ 37.59万 - 项目类别:
Novel mechanism of action as therapeutic strategy for optic neuritis
作为视神经炎治疗策略的新作用机制
- 批准号:
8675259 - 财政年份:2012
- 资助金额:
$ 37.59万 - 项目类别:
Novel mechanism of action as therapeutic strategy for optic neuritis
作为视神经炎治疗策略的新作用机制
- 批准号:
8511676 - 财政年份:2012
- 资助金额:
$ 37.59万 - 项目类别:
Novel mechanism of action as therapeutic strategy for optic neuritis
作为视神经炎治疗策略的新作用机制
- 批准号:
8366675 - 财政年份:2012
- 资助金额:
$ 37.59万 - 项目类别:
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