Layer-specific imaging of retinal degeneration

描述(申请人提供)：视网膜色素变性(RP)是一组遗传性疾病，以进行性光感受器退化为特征，影响全球150万人。位于视网膜两侧的血管(脉络膜和视网膜)层和其他(双极和神经节)细胞层也会受到影响。目前RP的临床评估在很大程度上依赖于视觉测试。能够检测特定于层的细胞和血管变化的非侵入性成像技术将使客观的早期检测、纵向疾病分期、治疗干预监测以及对潜在病理生理学的更好理解成为可能。基于光学的视网膜成像技术可能会受到介质不透明(即白内障和玻璃体出血)的限制，这阻碍了对视网膜深层和血管的可视化。相比之下，磁共振成像(MRI)提供了无创的解剖、生理和功能图像，没有深度限制。然而，为视网膜MRI实现足够的空间分辨率仍然具有挑战性。在这项计划中，我们将开发新的解剖、生理和功能MRI来在60x60x500 5m的高度分辨视网膜的不同层，并通过纵向研究皇家外科医生学院(RCS)大鼠视网膜进行性的、层特异性的视网膜变性来大力测试这一能力，这是一个已建立的人类RP模型。与公共健康相关：这项建议概述了新的MRI方法的开发、交叉验证和应用，以解决极高空间分辨率下视网膜的结构、生理和功能层特异性。它具有很强的临床意义和潜在的影响，因为它可以提供1)视网膜变性的早期标志物，用于监测治疗干预和2)视网膜和脉络膜血流和氧合是如何调节的，以及视网膜变性是如何影响这两个血管和它们所伴随的神经组织的。这些动物研究的数据应该会推动这些研究领域的发展，为视网膜研究开辟新的途径，并为未来的人类研究奠定基础。

DESCRIPTION (provided by applicant): Retinitis pigmentosa (RP) is a group of inherited diseases marked by progressive photoreceptor degeneration, affecting 1.5 million people worldwide. The vascular (choroidal and retinal) layers located on either side of the retina and other (bipolar and ganglion) cell layers are also affected. Current clinical assessment of RP relies heavily on visual testing. Non-invasive imaging technologies capable of detecting layer-specific cellular and vascular changes would enable objective early detection, longitudinal disease staging, monitoring of therapeutic intervention, and improved understanding of the underlying pathophysiology. Optical-based retinal imaging techniques can be limited by media opacity (i.e., cataracts and vitreous hemorrhages) which precludes visualization of deep retinal layers and vessels. In contrast, magnetic resonance imaging (MRI) provides non-invasive images of anatomy, physiology and function without depth limitation. Achieving sufficient spatial resolution for retinal MRI, however, remains challenging. In this proposal, we will develop novel anatomical, physiologic and functional MRI to resolve various layers of the retina at 60x60x500 5m, and vigorously test this capability by longitudinally investigating progressive, layer-specific retinal degeneration in the Royal-College-of-Surgeon (RCS) rat retinas, an established model of human RP. PUBLIC HEALTH RELEVANCE: This proposal outlines the development, cross-validation and application of novel MRI approaches to resolve structural, physiological and functional laminar specificity of the retina at very high spatial resolution. It has strong clinical significance and potential impact to the field in that it can provide 1) an early marker of retinal degeneration and for monitoring therapeutic intervention and 2) powerful insights into how retinal and choroidal blood flow and oxygenation are regulated and how retinal degeneration affects the two vasculatures and the neural tissues they subserve. Data from these animal studies should advance these areas of research, open up new avenues for retinal research, and lay the foundation for future human studies.