MR STUDIES OF EXPERIMENTAL RETINOPATHY OF PREMATURITY

描述（改编自申请人摘要）： 视网膜新生血管的ROP是不完全了解，虽然 缺氧被认为是其发展的关键。 长期 本研究的目的是更好地了解缺氧在 视网膜新生血管，以便更有效地预防，诊断 并且可以开发治疗策略。 在过去的融资中 在此期间，开发了一种新的MRI方法来非侵入性地映射 氧合速率沿着视网膜的二维范围。 这 方法显示，一个异常缓慢的视网膜氧合率存在于 在ROP发展之前的视网膜。 这种缓慢的氧化速率是 符合缺氧，但它还不能明确地解释为 缺氧的测量。 本提案试图确认两个假设： (1)异常缓慢的氧合提供了一种间接的， 缺氧的测量和（2）这种MRI方法具有潜在的临床意义 用于指导辅助供氧治疗的实用程序。 三个具体目标将 使用这种MRI方法和ROP的新生大鼠模型来解决：（1） 确定视网膜前玻璃体视网膜氧含量 正常和病理状态下的张力和氧合速率;（2） 以确定是否发生在视网膜氧合的变化， 补充供氧治疗与补充剂量呈线性关系， 在新血管形成过程中;以及（3）确定 在新生血管形成之前测量的视网膜氧合率和 需要补充氧气以防止血管内皮生长因子 （VEGF）上调和新血管形成。 拟议的研究将奠定 为类似MRI实验的最终临床评价奠定基础 在人类ROP中。 这项工作可能会产生广泛的影响，超出ROP，因为异常 血管生长是其他设盲的常见病理生物学事件 糖尿病性视网膜病变等。

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.