Department of Ophthalmology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Section of Research Resources, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Front Biosci (Landmark Ed). 2024 Nov 13;29(11):380. doi: 10.31083/j.fbl2911380.
Age-related macular degeneration (AMD) is the most common cause of vision loss in people above the age of 50, affecting approximately 10% of the population worldwide and the incidence is rising. Hyperreflective foci (HRF) are a major predictor of AMD progression. The purpose of this study was to use the sodium iodate mouse model to study HRF formation in retinal degeneration.
Sodium iodate (NaIO) treated rodents were studied to characterize HRF. 3-month-old male wild-type (WT) C57Bl/6J mice were injected with phosphate-buffered saline (PBS) or varying doses of NaIO (15-60 mg/kg). Optical Coherence Tomography (OCT) images were collected at baseline and several days post-NaIO injection. Retinal thicknesses were measured using Bioptigen software. Seven days post-injection, eyes were prepared for either transmission electron microscopy (TEM), Hematoxylin & Eosin (H&E), or immunofluorescence.
OCT imaging of the mice given higher doses of NaIO revealed HRF formation in the neural retina (n = 4). The amount of HRF correlated with the degree of retinal tissue loss. H&E and TEM imaging of the retinas seven days post-NaIO injection revealed several pigmented bodies in multiple layers of the retina (n = 3-5). Immunofluorescence revealed that some pigmented bodies were positive for macrophage markers and an epithelial-to-mesenchymal transition marker, while all were retinal pigment epithelium (RPE) 65-negative (n = 4).
The data suggest that NaIO induces the formation of HRF in the outer retina and their abundance correlates with retinal tissue loss. The experiments in this study highlight NaIO as a clinically relevant model of intermediate AMD that can be used to study HRF formation and to discover new treatment targets.
年龄相关性黄斑变性（AMD）是 50 岁以上人群视力丧失的最常见原因，全球约有 10%的人口受到影响，且发病率正在上升。高反射焦点（HRF）是 AMD 进展的主要预测因素。本研究旨在使用碘酸钠小鼠模型研究视网膜变性中 HRF 的形成。
研究了碘酸钠（NaIO）处理的啮齿动物，以表征 HRF。将 3 月龄雄性野生型（WT）C57Bl/6J 小鼠注射磷酸盐缓冲盐水（PBS）或不同剂量的 NaIO（15-60mg/kg）。在基线和 NaIO 注射后几天采集光学相干断层扫描（OCT）图像。使用 Bioptigen 软件测量视网膜厚度。注射后 7 天，准备进行透射电子显微镜（TEM）、苏木精和伊红（H&E）或免疫荧光检查。
对接受较高剂量 NaIO 的小鼠进行 OCT 成像显示，在神经视网膜中形成 HRF（n=4）。HRF 的数量与视网膜组织丢失的程度相关。NaIO 注射后 7 天对视网膜进行 H&E 和 TEM 成像显示，视网膜的多个层中存在多个色素体（n=3-5）。免疫荧光显示，一些色素体阳性巨噬细胞标志物和上皮-间充质转化标志物，而所有色素体均为视网膜色素上皮（RPE）65 阴性（n=4）。
数据表明，NaIO 诱导外视网膜 HRF 的形成，其丰度与视网膜组织丢失相关。本研究中的实验突出了 NaIO 作为一种有临床相关性的中间型 AMD 模型，可用于研究 HRF 的形成并发现新的治疗靶点。
