Sex and Gender Supplement to Elastase and Elastin Peptide Activity in Age-Related Macular Degeneration
Sex and Gender Supplement to Elastase and Elastin Peptide Activity in Age-Related Macular Degeneration
批准号:
10334019
负责人:
Baerbel Rohrer
金额:
$15.03万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-01-01 至 2024-12-31
关键词:
AccountingAdministrative SupplementAffectAge of OnsetAge related macular degenerationAntibodiesAntibody FormationBiologicalBlindnessBruch&aposs basal membrane structureCenters for Disease Control and Prevention (U.S.)ComplementComplement ActivationComplement-Dependent CytotoxicityDataData AnalysesData SetDatabasesDevelopmentDiagnosisDiseaseDisease ProgressionElastasesElastinEventExhibitsExtracellular MatrixEyeFemaleGenderGene ExpressionGoalsGrantHealthHealthcareHumanImmune responseInflammatoryIntraperitoneal InjectionsKnowledgeMeasuresModelingMusOxidative StressParentsPathogenesisPathologyPatientsPeptide HydrolasesPeptidesPrevalenceProductionPulmonary EmphysemaResearchRetinal DegenerationRiskRoleSample SizeSerine ProteaseSex DifferencesStressStructureStructure of retinal pigment epitheliumTestingTherapeuticTherapeutic EffectThinnessTransgenic MiceTrypsinUnited Statesalpha 1-Antitrypsinalpha 1-Antitrypsin Deficiencyantibody-dependent cell cytotoxicitybasebiological sexelastase inhibitorexperimental studyinhibitor/antagonistmalemouse modelnovelpersonalized approachresponsesextool
中文摘要
摘要
英文摘要
ABSTRACT
This is an application for an Administrative Supplement for Research on Sex/Gender Influences (NOT-OD-20-
049). The overall goals of the parent R01 (5R01EY030072-02) are to investigate the roles of elastase and
elastin fragments in retina pigment epithelial function (RPE) and health, and how it may be modified in the
presence of the elastase inhibitor, alpha-1 anti-trypsin (A1-AT). The overall hypothesis of the parental grant is
that age- and/or stress-dependent increase in elastase activity leading to elastin degradation and coordinated
production of (anti) α-elastin antibodies are early evens in AMD. As AMD is a disease with greater prevalence
in females, we further hypothesize that elastase activity may vary between sex leading to differences in AMD
development. Therefore, we propose to use increased sample size within an AMD mouse model for retinal
degeneration, as well as additional analysis of a retrospective patient database to measure for differences
between sex. We have developed three specific aims to complement those of the parental grant, allowing for
analysis of biological differences of sex in AMD pathobiology. The first aim will characterize sex differences in
elastin turnover, production of α-elastin antibodies and evidence of ADCC (antibody-dependent cellular
cytotoxicity) and CDC (complement-dependent cytotoxicity) within a mouse model of retinal degeneration. The
second aim will test the hypothesis that α-elastin antibodies in female mice have increased augmented
pathology in a mouse model of RPE damage. For specific aim 3, we will test the hypothesis that A1-AT therapy
results in sex-differences in onset of AMD in human and mouse subjects. Aims 1-3 will utilize experiments
proposed in the parental grant to further explore differences in structure, function, and gene expression
between sex. To analyze sex differences on the onset of AMD in the presence of A1-AT therapy, we will
analyze differences between males and females in the MarketScan Database. This grant supplement will
provide much needed knowledge on how sex may affect differences in AMD pathology. This novel data will aid
in the development of AMD therapeutics and provide information needed to develop a more individualized
approach to health care which considers differences between sex.
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会议论文
Elastase and Elastin Peptide Activity in Age-Related Macular Degeneration
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批准号:10563120
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项目类别:
-
资助金额:$33.43万
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财政年份:2020
-
负责人:Baerbel Rohrer
-
依托单位:
Elastase and Elastin Peptide Activity in Age-Related Macular Degeneration
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批准号:10312122
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项目类别:
-
资助金额:$32.43万
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财政年份:2020
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负责人:Baerbel Rohrer
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依托单位:
Elastase and Elastin Peptide Activity in Age-Related Macular Degeneration
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批准号:9885803
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项目类别:
-
资助金额:$40.39万
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财政年份:2020
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负责人:Baerbel Rohrer
-
依托单位:
Elastase and Elastin Peptide Activity in Age-Related Macular Degeneration
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批准号:10077557
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项目类别:
-
资助金额:$32.43万
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财政年份:2020
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负责人:Baerbel Rohrer
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依托单位:
BLR&D Research Career Scientist Award for Dr. Barbel Rohrer
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批准号:10515291
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项目类别:
-
资助金额:$0.0万
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财政年份:2019
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负责人:Baerbel Rohrer
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依托单位:
BLR&D Research Career Scientist Award for Dr. Barbel Rohrer
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批准号:10293580
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项目类别:
-
资助金额:$0.0万
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财政年份:2019
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负责人:Baerbel Rohrer
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依托单位:
BLR&D Research Career Scientist Award for Dr. Barbel Rohrer
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批准号:10047234
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项目类别:
-
资助金额:$0.0万
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财政年份:2019
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负责人:Baerbel Rohrer
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依托单位:
RPE Cell Bystander Effects Contribute to AMD Pathology
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批准号:10015692
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项目类别:
-
资助金额:$0.0万
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财政年份:2016
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负责人:Baerbel Rohrer
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依托单位:
RPE Cell Bystander Effects Contribute to AMD Pathology
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批准号:10293593
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项目类别:
-
资助金额:$0.0万
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财政年份:2016
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负责人:Baerbel Rohrer
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依托单位:
RPE Cell Bystander Effects Contribute to AMD Pathology
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批准号:9137278
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项目类别:
-
资助金额:$0.0万
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财政年份:2016
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负责人:Baerbel Rohrer
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依托单位:
RPE Cell Bystander Effects Contribute to AMD Pathology
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批准号:10514599
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项目类别:
-
资助金额:$0.0万
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财政年份:2016
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负责人:Baerbel Rohrer
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依托单位:
ECT Implants for Factor H Delivery in Models of AMD
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批准号:8919367
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项目类别:
-
资助金额:$36.35万
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财政年份:2014
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负责人:Baerbel Rohrer
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依托单位:
ECT Implants for Factor H Delivery in Models of AMD
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批准号:9132253
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项目类别:
-
资助金额:$37.09万
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财政年份:2014
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负责人:Baerbel Rohrer
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依托单位:
ECT Implants for Factor H Delivery in Models of AMD
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批准号:8750307
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项目类别:
-
资助金额:$38.33万
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财政年份:2014
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负责人:Baerbel Rohrer
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依托单位:
Complement Factor H-based Therapeutic Strategies in Macular Degeneration
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批准号:10261459
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项目类别:
-
资助金额:$0.0万
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财政年份:2010
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负责人:Baerbel Rohrer
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依托单位:
Alternative Pathway of Complement Activation in Age-Related Macular Degeneration
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批准号:8500295
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项目类别:
-
资助金额:$30.17万
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财政年份:2010
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负责人:Baerbel Rohrer
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依托单位:
Complement Factor H Haplotypes and Smoking in Age-Related Macular Degeneration
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批准号:8181318
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项目类别:
-
资助金额:$0.0万
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财政年份:2010
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负责人:Baerbel Rohrer
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依托单位:
Complement Factor H-based Therapeutic Strategies in Macular Degeneration
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批准号:9394727
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项目类别:
-
资助金额:$0.0万
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财政年份:2010
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负责人:Baerbel Rohrer
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依托单位:
Complement Factor H Haplotypes and Smoking in Age-Related Macular Degeneration
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批准号:8916644
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项目类别:
-
资助金额:$0.0万
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财政年份:2010
-
负责人:Baerbel Rohrer
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依托单位:
Alternative Pathway of Complement Activation in Age-Related Macular Degeneration
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批准号:8288204
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项目类别:
-
资助金额:$31.75万
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财政年份:2010
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负责人:Baerbel Rohrer
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依托单位:
海外基金