The role of iris biomechanics and sex differences in primary angle-closure glaucoma
虹膜生物力学和性别差异在原发性闭角型青光眼中的作用
基本信息
- 批准号:10723800
- 负责人:
- 金额:$ 11.2万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-30 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:AcuteAddressAdrenergic AgentsAffectAgeAnatomyAnimal ModelAnimalsAnteriorAnti-CholinergicsAqueous HumorBasic ScienceBiomechanicsBlindnessCadaverCholinergic AgentsClinicalClinical ResearchClinical TrialsComputer ModelsDataDevelopmentDilatorDisparityElementsEngineeringEvaluationEyeFemaleFunctional disorderFutureGlaucomaHistologyHumanHybridsImageIndividualIrisLearningLightLinkMeasuresMechanicsMentorsModelingMorbidity - disease rateMuscleMuscle ContractionMydriasisOryctolagus cuniculusOutcomePathway interactionsPatientsPersonsPharmaceutical PreparationsPhasePhysiologic Intraocular PressurePhysiologicalPlayPrevalencePrimary Angle Closure GlaucomaPropertyProtocols documentationPublic HealthPupil light reflexRaceRecording of previous eventsRelaxationResearch PersonnelRiskRisk FactorsRoleSex DifferencesSphincterStudy SubjectTechniquesTestingTissuesTractionTrainingValidationWomananterior chamberbiomechanical testcareerclinical riskcomparison controlconstrictionhigh riskhuman subjectimprovedin vivolens inductionmalemedically necessary carepressurepreventrisk stratificationsexskillstherapeutic target
项目摘要
Primary angle-closure glaucoma (PACG) is a significant cause of irreversible blindness worldwide, affecting c.
17M people. PACG is more prevalent among women; unfortunately, the underlying reasons for this unequal
prevalence are unknown. Factors other than sex, such as anatomical deficits in the anterior chamber, race, and
age, are associated with PACG, with anatomical deficits being the accepted primary clinical criteria used to
assess PACG risk. However, several clinical trials have shown that such anatomical factors are surprisingly poor
predictors of PACG development, indicating the involvement of other unaccounted factors in PACG.
The pathophysiological mechanisms of PACG are closely related to the biomechanics of the iris. Specifically, in
pupillary block (PB), a key feature of PACG, contact between the iris and the lens induces a pressure gradient
between the anterior and posterior chambers. Subsequently, PB leads to occlusion of the outflow pathway (i.e.,
angle closure [AC]) by anterior deformation of the iris, with associated elevation of intraocular pressure and
potential glaucomatous vision loss. We and others have shown that by using pupillary reflexes (e.g., triggered
by light), one can non-invasively evaluate the biomechanical properties of the iris. Interestingly, in patients with
a history of PACG, the iris is stiffer compared to controls. However, the role of iris biomechanics in inducing AC
and PACG is unknown.
Our central hypothesis is that iris biomechanics plays a crucial, unappreciated role in developing PACG, based
on the natural connection between iridial deformations and iridial biomechanical properties. Therefore, this pro-
ject objective is to investigate the role of iris biomechanics in PACG through the evaluation of iridial biome-
chanical properties and mechanics of AC and PB. In addition, we will investigate sex-dependent differences in
iris biomechanics and their potential role in predisposing women to a higher risk of developing PACG.
This project s specific aims (SA) are: SA1 - Investigate sex differences in the biomechanical properties of the iris
using a hybrid in vivo/ex vivo approach in rabbits (K99 mentored phase). SA2 - Investigate sex differences in
biomechanical properties of the human iris using in vivo and ex vivo (cadaver) analyses. SA3 - Investigate bio-
mechanical conditions required to induce AC and PB, and their relation to sex and history of AC (R00). These
studies will provide an improved understanding of the pathophysiology of PACG and a unique opportunity to
combine engineering, basic science, and clinical research to address a significant public health issue.
During the mentored phase, the applicant will learn multiple foundational techniques, including in vivo animal
studies in rabbits, biomechanical analysis of active (muscular) tissue, histology, OCT imaging, and human sub-
ject studies. In addition, he will significantly expand his professional training through various mechanisms. The
skills and techniques learned during the mentored phase will build on the applicant s background in tissue bio-
mechanics and allow him to pursue a successful and impactful independent academic career.
原发性闭角型青光眼(Primary angle- closed glaucoma, PACG)是世界范围内不可逆性失明的重要原因。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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