Eye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, China; Zhejiang Provincial Key Laboratory of Ophthalmology, Hangzhou, 310009, Zhejiang, China.
Eye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, China; Zhejiang Provincial Key Laboratory of Ophthalmology, Hangzhou, 310009, Zhejiang, China.
Exp Eye Res. 2024 Oct;247:110050. doi: 10.1016/j.exer.2024.110050. Epub 2024 Aug 14.
Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the elderly population. Sodium iodate (NaIO), a stable oxidizing agent, has been injected to establish a reproducible model of oxidative stress-induced RPE and photoreceptor death. The aim of our study was to evaluate the morphological and molecular changes of retina and retinal pigment epithelium (RPE)-choroid in NaIO-treated mouse using multimodal fundus imaging and label-free quantitative proteomics analysis. Here, we found that following NaIO injection, retinal degeneration was evident. Fundus photographs showed numerous scattered yellow-white speckled deposits. Optical coherence tomography (OCT) images indicated disruption of the retinal layers, damage of the RPE layer and accumulation of hyper-reflective matter in multiple layers of the outer retina. Widespread foci of a high fundus autofluorescence (FAF) signal were noticed. Fundus fluorescein angiography (FFA) revealed diffuse intense transmitted fluorescence mixed with scattered spot-like blocked fluorescence. Indocyanine green angiography (ICGA) presented punctate hyperfluorescence. Due to the atrophy of the RPE and Bruch's membrane and choroidal capillary complex, the larger choroidal vessels become more prominent in ICGA and optical coherence tomography angiography (OCTA). Transmission electron microscope (TEM) illustrated abnormal material accumulation and damaged mitochondria. Bioinformatics analysis of proteomics revealed that the differentially expressed proteins participated in diverse biological processes, encompassing phototransduction, NOD-like receptor signaling pathway, phagosome, necroptosis, and cell adhesion molecules. In conclusion, by multimodal imaging, we described the phenotype of NaIO-treated mouse model mimicking oxidative stress-induced RPE and photoreceptor death in detail. In addition, proteomics analysis identified differentially expressed proteins and significant enrichment pathways, providing insights for future research, although the exact mechanism of oxidative stress-induced RPE and photoreceptor death remains incompletely understood.
年龄相关性黄斑变性（AMD）是老年人不可逆性视力丧失的主要原因。碘酸钠（NaIO）是一种稳定的氧化剂，已被用于建立氧化应激诱导的 RPE 和光感受器死亡的可复制模型。我们的研究目的是使用多模态眼底成像和无标记定量蛋白质组学分析来评估 NaIO 处理的小鼠视网膜和视网膜色素上皮（RPE）脉络膜的形态和分子变化。在这里，我们发现，在 NaIO 注射后，视网膜变性是明显的。眼底照片显示出许多散在的黄白色斑点状沉积物。光学相干断层扫描（OCT）图像表明视网膜层的破坏，RPE 层的损伤以及外视网膜的多个层中高反射物质的积累。广泛注意到高眼底自发荧光（FAF）信号的焦点。眼底荧光血管造影（FFA）显示弥漫性强透射荧光混合有散在点状阻塞荧光。吲哚菁绿血管造影（ICGA）呈现点状高荧光。由于 RPE 和 Bruch 膜和脉络膜毛细血管复合物的萎缩，在 ICGA 和光学相干断层扫描血管造影（OCTA）中较大的脉络膜血管变得更加突出。透射电子显微镜（TEM）说明了异常物质的积累和受损的线粒体。蛋白质组学的生物信息学分析表明，差异表达的蛋白质参与了多种生物学过程，包括光转导，NOD 样受体信号通路，吞噬体，坏死性凋亡和细胞粘附分子。总之，通过多模态成像，我们详细描述了模仿氧化应激诱导的 RPE 和光感受器死亡的 NaIO 处理的小鼠模型的表型。此外，蛋白质组学分析鉴定了差异表达的蛋白质和显著富集的途径，为未来的研究提供了思路，尽管氧化应激诱导的 RPE 和光感受器死亡的确切机制仍不完全清楚。
