University of Poitiers, Laboratoire de Neurosciences Expérimentales et Cliniques, Equipe Thérapie cellulaire dans les pathologies cérébrales, Poitiers, F-86073, France; INSERM, U1084, Laboratoire de Neurosciences Expérimentales et Cliniques, Equipe Thérapie cellulaire dans les pathologies cérébrales, Poitiers, F-86022, France; CHU Poitiers, Poitiers, F-86021, France.
University of Poitiers, Laboratoire de Neurosciences Expérimentales et Cliniques, Equipe Thérapie cellulaire dans les pathologies cérébrales, Poitiers, F-86073, France; INSERM, U1084, Laboratoire de Neurosciences Expérimentales et Cliniques, Equipe Thérapie cellulaire dans les pathologies cérébrales, Poitiers, F-86022, France; Laboratoires THEA, Clermont-Ferrand, France.
Exp Eye Res. 2024 Sep;246:109999. doi: 10.1016/j.exer.2024.109999. Epub 2024 Jul 10.
Age-related macular degeneration (AMD) is characterized by visual impairment observed in elderly population. Two forms of the disease are generally described, the atrophic (AMDa) and exudative forms (AMDe). Up until now, no curative treatment is available for this disease. The retinal pigment epithelium (RPE) plays a central role in the pathogenesis of age-related macular degeneration. Here, involvement of RPE dysfunction in AMD onset and progression was analyzed by a comparison of transcriptome profiles of hiPSC-RPE derived from healthy individuals or individuals affected by AMDa or AMDe. The analysis highlighted almost 1000 genes differentially expressed between the three comparison groups. Among these genes, 33 genes were already known to be involved in AMD pathogenesis. To establish an AMD genetic signature, we focused on genes differentially expressed in both AMDa/e cell lines compared to control cells and focused on the three genes (ABCA1, RPN2, RB1CC1) that were related to lipidic homeostasis. Differences in level expression of these three genes are found not only in control and AMDa/e cell lines, but also between AMDa and AMDe populations.
年龄相关性黄斑变性（AMD）的特征是在老年人群中观察到的视力障碍。通常描述两种疾病形式，萎缩性（AMDa）和渗出性形式（AMDe）。到目前为止，这种疾病还没有有效的治疗方法。视网膜色素上皮（RPE）在年龄相关性黄斑变性的发病机制中起着核心作用。在这里，通过比较源自健康个体或受 AMDa 或 AMDe 影响的个体的 hiPSC-RPE 的转录组谱，分析了 RPE 功能障碍在 AMD 发病和进展中的作用。该分析突出了三个比较组之间差异表达的近 1000 个基因。在这些基因中，有 33 个基因已被证明与 AMD 发病机制有关。为了建立 AMD 的遗传特征，我们专注于在 AMDa/e 细胞系与对照细胞相比差异表达的基因，并关注与脂质稳态相关的三个基因（ABCA1、RPN2、RB1CC1）。这三个基因的表达水平差异不仅存在于对照和 AMDa/e 细胞系之间，而且存在于 AMDa 和 AMDe 群体之间。
