Department of Pathology, UC San Diego, La Jolla, CA, USA.
Amydis, Inc., San Diego, CA.
J Alzheimers Dis. 2022;88(3):1137-1145. doi: 10.3233/JAD-220314.
Neurodegenerative diseases are widespread yet challenging to diagnose and stage antemortem. As an extension of the central nervous system, the eye harbors retina ganglion cells vulnerable to degeneration, and visual symptoms are often an early manifestation of neurodegenerative disease.
Here we test whether prion protein aggregates could be detected in the eyes of live mice using an amyloid-binding fluorescent probe and high-resolution retinal microscopy.
We performed retinal imaging on an experimental mouse model of prion-associated cerebral amyloid angiopathy in a longitudinal study. An amyloid-binding fluorophore was intravenously administered, and retinal imaging was performed at timepoints corresponding to early, mid-, and terminal prion disease. Retinal amyloid deposits were quantified and compared to the amyloid load in the brain.
We report that by early prion disease (50% timepoint), discrete fluorescent foci appeared adjacent to the optic disc. By later timepoints, the fluorescent foci surrounded the optic disc and tracked along retinal vasculature.
The progression of perivascular amyloid can be directly monitored in the eye by live imaging, illustrating the utility of this technology for diagnosing and monitoring the progression of cerebral amyloid angiopathy.
神经退行性疾病广泛存在，但难以在生前进行诊断和分期。作为中枢神经系统的延伸，眼睛拥有易发生变性的视网膜神经节细胞，而视觉症状往往是神经退行性疾病的早期表现。
本研究旨在使用一种与淀粉样蛋白结合的荧光探针和高分辨率视网膜显微镜，检测活体小鼠眼睛中是否存在朊病毒蛋白聚集。
我们对朊病毒相关脑淀粉样血管病的实验性小鼠模型进行了纵向视网膜成像研究。静脉内给予与淀粉样蛋白结合的荧光染料，并在对应于朊病毒疾病早期、中期和晚期的时间点进行视网膜成像。定量分析视网膜淀粉样沉积物，并与大脑中的淀粉样蛋白负荷进行比较。
我们报告称，在早期朊病毒疾病（50%时间点）时，视神经盘旁出现离散的荧光焦点。在稍后的时间点，荧光焦点环绕视神经盘并沿视网膜血管追踪。
通过活体成像可以直接监测眼内血管周围淀粉样蛋白的进展，这表明该技术可用于诊断和监测脑淀粉样血管病的进展。
