MR STUDIES OF EXPERIMENTAL RETINOPATHY OF PREMATURITY

描述(改编自申请人摘要)：发病机制 ROP中的视网膜新生血管尚不完全清楚，尽管 低氧被认为是其发展的关键。长期的 本研究的目的是为了更好地了解低氧在脑损伤中的作用 让视网膜新生血管更有效地预防、诊断 治疗策略可能会被开发出来。在之前的资助期间 Period开发了一种新的MRI方法来非侵入性地定位 沿视网膜二维范围的氧合率。这 方法显示，视网膜氧合率异常缓慢的 ROP发生前的视网膜。这种缓慢的氧合速度是 与缺氧一致，但还不能明确地解释为 测量缺氧程度。本建议旨在确认两个假设： (1)异常缓慢的氧合提供了一种间接的、但特异的 (2)该MRI方法具有潜在的临床应用价值。 指导辅助氧疗的效用。三个具体目标将 使用这种MRI方法和ROP的新生大鼠模型：(1) 确定视网膜前玻璃体视网膜氧含量与 正常和病理条件下的张力和氧合率；(2) 以确定视网膜氧合的变化是否发生在 补充氧气治疗与补充剂量呈线性关系，并随补充剂量的增加而变化 在新生血管形成过程中；以及(3)确定 新生血管形成前的视网膜氧合率和血管生成水平 预防血管内皮生长因子所需的补充氧气 (血管内皮生长因子)上调与新生血管形成。拟议的研究将 为类似磁共振实验的最终临床评估奠定基础 在人类ROP中。这项工作可能会产生比ROP更广泛的影响，因为 血管生长是其他致盲的常见病理生物学事件 疾病，如糖尿病视网膜病变。

DESCRIPTION (Adapted from applicant's abstract): The pathogenesis of retinal neovascularization in ROP is incompletely understood, although hypoxia is thought to be critical for its development. The long-term objective of this research is to understand better the role of hypoxia in retinal neovascularization so that more effective preventative, diagnostic and therapeutic strategies may be developed. During the previous funding period a novel MRI method was developed to non-invasively map the oxygenation rate along the two-dimensional extent of the retina. This method showed that an unusually slow retinal oxygenation rate was present in retinas before the development of ROP. This slow oxygenation rate is consistent with hypoxia, but it cannot yet be interpreted unambiguously as a measure of hypoxia. The present proposal seeks to confirm two hypotheses: (1) that abnormally slow oxygenation provides an indirect, yet specific measure of hypoxia and (2) that this MRI method has potential clinical utility for directing supplemental oxygen therapy. Three specific aims will be addressed using this MRI method and a newborn rat model of ROP: (1) to determine the association between the preretinal vitreous retinal oxygen tension and oxygenation rate under normal and pathological conditions; (2) to determine if the change in retinal oxygenation that occurs during supplemental oxygen treatment is linear with supplemental dose and evolves during neovascularization; and (3) to determine the association between the retinal oxygenation rate measured before neovascularization and the level of supplemental oxygen needed to prevent vascular endothelial growth factor (VEGF) upregulation and neovascularization. The proposed studies will lay the groundwork for eventual clinical evaluation of similar MRI experiments in human ROP. This work may have broad impact beyond ROP since abnormal blood vessel growth is a common pathobiologic event for other blinding disorders, such as diabetic retinopathy.