PDF(Pubmed)
Abstract：
Aging is the main risk factor for age-related macular degeneration (AMD), a retinal neurodegenerative disease that leads to irreversible blindness, particularly in people over 60 years old. Retinal pigmented epithelium (RPE) atrophy is an AMD hallmark. Genome-wide chromatin accessibility, DNA methylation, and gene expression studies of AMD and control RPE demonstrate epigenomic/transcriptomic changes occur during AMD onset and progression. However, mechanisms by which molecular alterations of normal aging impair RPE function and contribute to AMD pathogenesis are unclear. Here, we specifically interrogate the RPE translatome with advanced age and across sexes in a novel RPE reporter mouse model. We find differential age- and sex- associated transcript expression with overrepresentation of pathways related to inflammation in the RPE. Concordant with impaired RPE function, the phenotypic changes in the aged translatome suggest that aged RPE becomes immunologically active, in both males and females, with some sex-specific signatures, which supports the need for sex representation for in vivo studies.
摘要：
衰老是年龄相关性黄斑变性(AMD)的主要危险因素,导致不可逆失明的视网膜神经退行性疾病,尤其是60岁以上的人。视网膜色素上皮(RPE)萎缩是AMD的标志。全基因组染色质可及性，DNA甲基化，AMD和对照RPE的基因表达研究表明，在AMD发作和进展期间会发生表观基因组/转录组变化。然而,正常衰老的分子改变损害RPE功能并导致AMD发病的机制尚不清楚。这里,我们在一个新的RPE记者小鼠模型中特别询问了年龄和性别的RPE翻译组。我们发现年龄和性别相关的转录物表达差异，与RPE中炎症相关的途径过度表达。与受损的RPE功能一致，老年翻译组的表型变化表明老年RPE具有免疫活性，在男性和女性中，有一些特定性别的签名，这支持了体内研究对性别代表的需求。
