Mechanistic-Based Non-Invasive Assessment of Retinal Damage in HAART Era

摘要 我们提案的目标是定义过早衰老对艾滋病毒的影响 人类眼睛上的血清阳性受试者。抗逆转录病毒疗法已经戏剧性地 提高艾滋病毒阳性受试者的预期寿命。研究表明，HIV+受试者 经历与年龄相关的变化比年龄匹配的艾滋病毒同龄人早10-15年。这个 人类视网膜为了解中枢神经系统的某一部分提供了一扇独特的窗口 (CNS)。目前，还没有监测衰老对中枢神经系统影响的生物标志物。 次要目标是开发一种针对中枢神经系统的替代生物标记物 损坏。在本提案中，我们将使用自适应光学(AO)成像来记录圆锥体 光感受器密度和视网膜血管形态计量学。我们的初步数据显示 HIV阳性受试者的视锥感光细胞密度较低。其他证据表明 微血管系统的变化可能与年龄有关。我们还将获得 OCT血管成像和代谢数据的无创血管参数 眼睛的终身荧光测量(Flio)。我们将使用颈动脉内膜-中层 作为心血管替代生物标志物的厚度。此外，我们还将能够访问 其他可能的生物衰老指标(端粒长度、线粒体常见 缺失、氧化应激和DNA甲基化的最终产物) 与HNRC的合作。通过结合AO成像、OCT血管成像和Flio 使用我们已建立的结构数据(SD-OCT等)和假定的老龄化措施 可以研究过早衰老对眼睛的影响。这些数据将与 神经行为、免疫学和医学数据由我们的合作者在 HNRC。我们计划开发临床可靠的评估工具，用于风险评估 过早衰老。我们将确定这些评估工具的预测能力 借助生物统计学模型。

ABSTRACT The goal of our proposal is to define the impact of premature aging in HIV seropositive subjects on the human eye. Antiretroviral therapy has dramatically improved the life expectancy of HIV+ subjects. Research indicates that HIV+ subjects experience age-related changes 10-15 years earlier than age-matched HIV- peers. The human retina offers a unique window into a section of the central nervous system (CNS). Currently, there is no biomarker for monitoring the effect of aging on the CNS. The secondary goal is the development of a surrogate biomarker in the eye for CNS damage. In this proposal we will use adaptive optical (AO) imaging to document cone photoreceptor density and retinal vascular morphometry. Our preliminary data suggests that HIV+ subjects have lower cone photoreceptor density. Other evidence indicates that changes to the microvasculature may be age-related. We will additionally acquire non-invasive vascular parameter using OCT angiography and metabolic data through lifetime fluorescence measurement in the eye (FLIO). We will use Carotid intima-media thickness as a cardiovascular surrogate biomarker. In addition, we will have access to other putative measures of biological aging (telomere length, mitochondrial common deletion, end-products of oxidative stress and DNA methylation) through the collaboration with the HNRC. By combining AO imaging, OCT angiography, and FLIO with our established structural data (SD-OCT, etc.) and putative measures of aging we can study the impact of premature aging on the eye. The data will be correlated with neurobehavioral, immunological and medical data collected by our collaborators at the HNRC. We plan to develop clinical reliable evaluation tools for risk assessment of premature aging. We will determine the prognostic capabilities of these evaluation tools with the help of biostatistical modeling.