Transocular detection of premotor Parkinson’s disease via retinal neurovascular coupling through functional OCT angiography

Kaiyuan Liu, Ruixue Wang, Longqian Huang, Huiying Zhang, Mengqin Gao, Bin Sun, Yizhou Tan, Juan Ye, Zhihua Ding, Ying Gu, Shaomin Zhang, Peng Li
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Abstract

The early detection of premotor Parkinson’s disease (PD) is important for initiating neuroprotective interventions prior to the widespread and irreversible loss of dopaminergic (DAergic) neurons. We propose a novel optical functional approach for detecting premotor PD from the retina by using functional OCT angiography (fOCTA) to measure PD-related changes in retinal neurovascular coupling (rNVC) at the capillary level, termed fOCTA-rNVC. We demonstrated that, likely due to the retinal DAergic degeneration, functional rNVC was attenuated and delayed in premotor PD mice, whereas no significant change in the retinal structure was found. Furthermore, the administration of levodopa reversed PD-related rNVC attenuation in premotor PD mice, whereas no recovery in ageing-related attenuation in aged mice without significant DAergic deficits was observed. On the basis of the levodopa recoverability of attenuated capillary rNVC, we achieved a remarkable accuracy of ∼100% in detecting premotor PD mice with ∼14.1% loss of midbrain DAergic neurons. These findings suggest that fOCTA-rNVC can be applied for the noninvasive and accurate detection of premotor PD, offering a cost-effective solution with improved accessibility and convenience for large-scale screening.
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通过功能性光学视网膜血管造影(OCT angiography)的视网膜神经血管耦合,经眼检测运动前帕金森病
在多巴胺能(DAergic)神经元出现广泛且不可逆的丧失之前,早期检测帕金森病(PD)的运动前期对于启动神经保护干预措施非常重要。我们提出了一种从视网膜检测运动前痴呆症的新型光学功能方法,利用功能性 OCT 血管造影术(fOCTA)在毛细血管水平测量痴呆症相关的视网膜神经血管耦合(rNVC)变化,称为 fOCTA-rNVC。我们发现,可能是由于视网膜DA能变性,运动前期帕金森病小鼠的功能性rNVC减弱并延迟,而视网膜结构未发现明显变化。此外,左旋多巴可逆转运动前期帕金森病小鼠与帕金森病相关的rNVC衰减,而在无明显DA能缺陷的老年小鼠中,未观察到与衰老相关的衰减恢复。根据左旋多巴对毛细血管rNVC衰减的可恢复性,我们在检测中脑DA能神经元缺失14.1%的运动前期PD小鼠方面达到了惊人的100%的准确率。这些研究结果表明,fOCTA-rNVC 可用于无创、准确地检测运动前期帕金森病,为大规模筛查提供了一种具有成本效益的解决方案,并提高了可及性和便利性。
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