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

• 批准号: 10723800
• 负责人: Babak Naghizadeh Safa
• 金额: $ 11.2万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/10723800
• 关键词: Acute; Address; Adrenergic Agents; Affect; Age; Anatomy; Animal Model; Animals; Anterior; Anti-Cholinergics; Aqueous Humor; Basic Science; Biomechanics; Blindness; Cadaver; Cholinergic Agents; Clinical; Clinical Research; Clinical Trials; Computer Models; Data; Development; Dilator; Disparity; Elements; Engineering; Evaluation; Eye; Female; Functional disorder; Future; Glaucoma; Histology; Human; Hybrids; Image; Individual; Iris; Learning; Light; Link; Measures; Mechanics; Mentors; Modeling; Morbidity - disease rate; Muscle; Muscle Contraction; Mydriasis; Oryctolagus cuniculus; Outcome; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Phase; Physiologic Intraocular Pressure; Physiological; Play; Prevalence; Primary Angle Closure Glaucoma; Property; Protocols documentation; Public Health; Pupil light reflex; Race; Recording of previous events; Relaxation; Research Personnel; Risk; Risk Factors; Role; Sex Differences; Sphincter; Study Subject; Techniques; Testing; Tissues; Traction; Training; Validation; Woman; anterior chamber; biomechanical test; career; clinical risk; comparison control; constriction; high risk; human subject; improved; in vivo; lens induction; male; medically necessary care; pressure; prevent; risk stratification; sex; skills; therapeutic target

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。