权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Cross-species vascular anatomy and sensitivity to intraocular pressure in glaucoma

青光眼的跨物种血管解剖学和对眼压的敏感性

基本信息

批准号：
10211782
负责人：
Tatjana Claudia Jakobs
金额：
$ 56.85万
依托单位：
MASSACHUSETTS EYE AND EAR INFIRMARY
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 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10211782
关键词：
3-Dimensional Acute Address Affect Anastomosis - action Anatomy Angiography Architecture Area Automobile Driving Autopsy Basement membrane Biomechanics Blindness Blood Vessels Blood capillaries Blood flow Characteristics Chronic Clinical Collagen Connective Tissue Contralateral Data Deposition Development Diffuse Disease Dyes Eye Fluorescent Dyes Glaucoma Histologic Human Image Immunohistochemistry In Situ Injections Ischemia Knowledge Label Link Maps Measurement Measures Mechanics Modeling Monkeys Morphology Mus Neuropathy Open-Angle Glaucoma Optic Disk Optic Nerve Optical Coherence Tomography Pathologic Pathology Pattern Perfusion Physiologic Intraocular Pressure Predisposition Primates Property Resolution Risk Factors Role Scotoma Shelter facility Solid Source Stenosis Structure Techniques Testing Time Tissues Variant Vascular Diseases Vascular blood supply Weight-Bearing state axon injury central retinal artery clinical imaging clinical phenotype ex vivo imaging experimental study high intraocular pressure imaging modality in vivo insight model building nerve injury relating to nervous system

项目摘要

SUMMARY Vascular dysfunction, with or without elevated intraocular pressure (IOP), is believed to be an important risk factor in glaucoma and other neuropathies. However, the link between vascular dysfunction and the mechanisms leading to the characteristic visual field defects in glaucoma is not fully understood. This is partly due to the lack of a solid quantitative understanding of the 3D architecture of the vasculature of the optic nerve head (ONH), its anatomical relationship with the load-bearing connective tissues, and how it is affected by IOP. Our overarching hypothesis is that features of the vasculature and its relationship with the connective tissues predispose certain ONH regions to compromised perfusion and that this susceptibility is amplified by elevated IOP. To test this hypothesis, we will sequentially collect in vivo, ex vivo, and histological 3D morphological and biomechanical data on vascular and connective tissues of the ONH in normal eyes and in eyes with experimental glaucoma (EG). We will focus on the critical lamina cribrosa (LC) region in three species: human, monkey (closest model to human, collagenous LC), and mouse (most used model, no collagenous LC). In Aim 1, we will map in 3D the vasculature and connective tissues of the ONHs of humans, monkeys, and mice, and analyze these maps quantitatively including by watershed analysis. We predict that zones of visual loss in early glaucoma will correspond to regions with the most vulnerable vascular supply, e.g., sparse capillaries with low connectivity and low perfusion redundancy. We postulate that, in primates, not all LC beams have a capillary, and conversely, that some capillaries are not within a robust collagen-rich beam. We will also address the clinically important question to which extent in vivo OCT angiography visualizes the smaller or deeper vessels inside the ONH. In Aim 2, we will perform ex vivo inflation tests on monkey and mouse eyes to quantify the effects of acute IOP elevation on vessel perfusion and biomechanics, and the LC beams support. Our preliminary data suggests that “unprotected” vessels may be particularly vulnerable to mechanical distortion, which could, in turn, affect blood flow. In Aim 3, we will characterize the effects of chronic IOP elevation on vessels and beams. Specifically, we will compare eyes before and after chronic IOP elevation (EG), and with the contralateral control. This will allow us to discern characteristics that pre-dispose an eye to glaucoma from those that are the result of the disease. We will test the hypothesis that the patterns of vessel sensitivity to elevated IOP in mice (that have only a glial lamina) are different from those in primates. Combining multiple imaging modalities across the same ONHs in three species will provide cross-verification of the techniques, and deeper insights into the role of LC collagenous beams supporting the ONH vasculature under normal and elevated IOP. These experiments will help identifying ONH features that predict susceptibility to neural injury and vision loss.

总结