Beijing Tongren Eye Center, Beijing Institute Of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Beijing Key Laboratory Of Ophthalmology And Visual Sciences, National Engineering Research Center For Ophthalmology, Beijing, China.
JAMA Ophthalmol. 2019 Jun 1;137(6):603-609. doi: 10.1001/jamaophthalmol.2019.0299.
Targeting the early pathogenic steps in Stargardt disease type 1 (STGD1) is critical to advance our understanding of this condition and to develop potential therapies. Lipofuscin precursors may accumulate within photoreceptors, leading to photoreceptor damage and preceding retinal pigment epithelial (RPE) cell death. Fluorescence adaptive optics scanning light ophthalmoscopy can provide autofluorescence (AF) images in vivo with microscopic resolution to elucidate the cellular origin of AF abnormalities in STGD1.
To study the spatial distribution of photoreceptor, RPE, and AF abnormalities in patients with STGD1 at a cellular level.
DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study using fluorescence adaptive optics scanning light ophthalmoscopy to compare the cones, rods, and RPE cells between 3 patients with STGD1 and 1 control individual. Imaging sessions were conducted at the University of Rochester. Further image analyses were performed at Beijing Tongren Eye Center and the University of Pittsburgh. Data were collected from August 2015 to February 2016, and analysis began in March 2016.
Structural appearance of cones, rods, and AF structures at different retinal locations.
Two women and 1 man with macular atrophy phenotype of STGD1 and visual acuity loss ranging from 20/30 to 20/150 and 1 woman without STGD1 with 20/20 visual acuity were analyzed. Cone and rod spacing was increased in all 3 patients at all locations where photoreceptors were detectable; most cones had a dark appearance. Autofluorescence was low contrast but contained structures consistent with RPE cells in the periphery. In the transition zone peripheral to the foveal atrophic lesion, the structural pattern of AF was more consistent with photoreceptors than RPE cells. The microscopic AF was disrupted within areas of clinically detectable atrophy.
Adaptive optics high-resolution images of cones, rods, and RPE cells at the leading disease front of STGD1 macular atrophy show an AF pattern that appears to colocalize with photoreceptors or may result from a combination of AF signals from both RPE cells and photoreceptors. This in vivo observation is consistent with histologic reports of fluorescence arising from photoreceptors in STGD1. The detection of bisretinoid accumulation in the photoreceptors may represent an early pathologic step in STGD1 and can provide an in vivo imaging tool to act as a biomarker of disease progression.
针对 1 型斯塔加特病（STGD1）的早期发病步骤对于深入了解这种疾病并开发潜在疗法至关重要。脂褐素前体可能在感光细胞内积累，导致感光细胞损伤，并先于视网膜色素上皮（RPE）细胞死亡。荧光自适应光学扫描激光检眼镜可以提供具有微观分辨率的体内自发荧光（AF）图像，以阐明 STGD1 中 AF 异常的细胞起源。
在细胞水平上研究 STGD1 患者的感光细胞、RPE 和 AF 异常的空间分布。
设计、设置和参与者：使用荧光自适应光学扫描激光检眼镜进行的横断面研究，比较了 3 名 STGD1 患者和 1 名对照个体的视锥细胞、视杆细胞和 RPE 细胞。成像会议在罗切斯特大学进行。进一步的图像分析在北京同仁眼中心和匹兹堡大学进行。数据收集于 2015 年 8 月至 2016 年 2 月，分析于 2016 年 3 月开始。
不同视网膜位置的视锥细胞、视杆细胞和 AF 结构的结构外观。
分析了 3 名具有 STGD1 黄斑萎缩表型和视力丧失范围从 20/30 到 20/150 的女性和 1 名男性患者，以及 1 名无 STGD1 但视力为 20/20 的女性。在所有可检测到感光器的位置，所有 3 名患者的视锥细胞和视杆细胞间距均增加；大多数视锥细胞外观较暗。自发荧光对比度较低，但包含在周边 RPE 细胞中一致的结构。在与中心凹萎缩病变相邻的周边过渡区，AF 的结构模式与感光器更一致，而不是 RPE 细胞。在临床上可检测到的萎缩区域内，微观 AF 被破坏。
STGD1 黄斑萎缩的主导疾病前沿的视锥细胞、视杆细胞和 RPE 细胞的自适应光学高分辨率图像显示出的 AF 模式似乎与感光器共定位，或者可能是由 RPE 细胞和感光器的 AF 信号组合而成。这种体内观察结果与 STGD1 中荧光来自感光器的组织学报告一致。在感光器中检测到双视黄醛的积累可能代表 STGD1 的早期病理步骤，并可提供一种体内成像工具作为疾病进展的生物标志物。
