Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences (SB RAS), Novosibirsk, Russia.
Cell Cycle. 2013 Jun 1;12(11):1745-61. doi: 10.4161/cc.24825. Epub 2013 May 6.
Pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly, remains poorly understood due to the paucity of animal models that fully replicate the human disease. Recently, we showed that senescence-accelerated OXYS rats develop a retinopathy similar to human AMD. To identify alterations in response to normal aging and progression of AMD-like retinopathy, we compared gene expression profiles of retina from 3- and 18-mo-old OXYS and control Wistar rats by means of high-throughput RNA sequencing (RNA-Seq). We identified 160 and 146 age-regulated genes in Wistar and OXYS retinas, respectively. The majority of them are related to the immune system and extracellular matrix turnover. Only 24 age-regulated genes were common for the two strains, suggestive of different rates and mechanisms of aging. Over 600 genes showed significant differences in expression between the two strains. These genes are involved in disease-associated pathways such as immune response, inflammation, apoptosis, Ca ( 2+) homeostasis and oxidative stress. The altered expression for selected genes was confirmed by qRT-PCR analysis. To our knowledge, this study represents the first analysis of retinal transcriptome from young and old rats with biologic replicates generated by RNA-Seq technology. We can conclude that the development of AMD-like retinopathy in OXYS rats is associated with an imbalance in immune and inflammatory responses. Aging alters the expression profile of numerous genes in the retina, and the genetic background of OXYS rats has a profound impact on the development of AMD-like retinopathy.
年龄相关性黄斑变性（AMD）的发病机制仍不清楚，这是老年人视力丧失的主要原因，因为缺乏能够完全复制人类疾病的动物模型。最近，我们发现加速衰老 OXYS 大鼠会发展出类似于人类 AMD 的视网膜病变。为了确定对正常衰老和 AMD 样视网膜病变进展的反应变化，我们通过高通量 RNA 测序（RNA-Seq）比较了来自 3 个月和 18 个月大的 OXYS 和对照 Wistar 大鼠的视网膜的基因表达谱。我们分别在 Wistar 和 OXYS 视网膜中鉴定出 160 个和 146 个与年龄相关的基因。其中大多数与免疫系统和细胞外基质周转有关。仅有 24 个与年龄相关的基因是两种菌株共有的，表明衰老的速度和机制不同。超过 600 个基因在两种菌株之间的表达存在显著差异。这些基因涉及与疾病相关的途径，如免疫反应、炎症、细胞凋亡、Ca（2+）稳态和氧化应激。通过 qRT-PCR 分析确认了选定基因的改变表达。据我们所知，这是首次使用 RNA-Seq 技术对具有生物学重复的年轻和老年大鼠的视网膜转录组进行分析。我们可以得出结论，AMD 样视网膜病变在 OXYS 大鼠中的发展与免疫和炎症反应失衡有关。衰老会改变视网膜中许多基因的表达谱，而 OXYS 大鼠的遗传背景对 AMD 样视网膜病变的发展有深远的影响。
