Layer-specific imaging of retinal degeneration

描述（由申请人提供）：视网膜色素变性（RP）是一组以进行性光感受器变性为特征的遗传性疾病，影响全球150万人。位于视网膜两侧的血管层（脉络膜和视网膜）和其他（双极和神经节）细胞层也受到影响。目前的临床评估主要依赖于视觉测试。能够检测层特异性细胞和血管变化的非侵入性成像技术将实现客观的早期检测，纵向疾病分期，监测治疗干预，并提高对潜在病理生理学的理解。基于光学的视网膜成像技术可能受到介质不透明（即白内障和玻璃体出血）的限制，这妨碍了视网膜深层层和血管的可视化。相比之下，磁共振成像（MRI）提供了无深度限制的非侵入性解剖、生理和功能图像。然而，为视网膜MRI实现足够的空间分辨率仍然具有挑战性。在本提案中，我们将开发新的解剖、生理和功能MRI来分辨60x60x500 5m的视网膜各层，并通过纵向研究皇家外科学院（RCS）大鼠视网膜的进行性、层特异性视网膜变性来大力测试这一能力，RCS是一种已建立的人类RP模型。公共卫生相关性：本提案概述了新型MRI方法的发展，交叉验证和应用，以非常高的空间分辨率解决视网膜的结构，生理和功能层流特异性。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记和监测治疗干预；2)视网膜和脉络膜血流量和氧合是如何调节的，以及视网膜变性如何影响它们所服务的两种血管和神经组织。这些动物研究的数据将推动这些领域的研究，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.