Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), Pr. Lavrentyeva 10, Novosibirsk 630090, Russia.
Int J Mol Sci. 2019 Sep 27;20(19):4804. doi: 10.3390/ijms20194804.
Age-related macular degeneration (AMD) is one of the main causes of vision impairment in the elderly. Autophagy is the process of delivery of cytoplasmic components into lysosomes for cleavage; its age-related malfunction may contribute to AMD. Here we showed that the development of AMD-like retinopathy in OXYS rats is accompanied by retinal transcriptome changes affecting genes involved in autophagy. These genes are associated with kinase activity, immune processes, and FoxO, mTOR, PI3K-AKT, MAPK, AMPK, and neurotrophin pathways at preclinical and manifestation stages, as well as vesicle transport and processes in lysosomes at the progression stage. We demonstrated a reduced response to autophagy modulation (inhibition or induction) in the OXYS retina at age 16 months: expression of genes , , , , , , and differed between OXYS and Wistar (control) rats. The impaired reactivity of autophagy was confirmed by a decreased number of autophagosomes under the conditions of blocked autophagosome-lysosomal fusion according to immunohistochemical analysis and transmission electron microscopy. Thus, the development of AMD signs occurs against the background of changes in the expression of autophagy-related genes and a decrease in autophagy reactivity: the ability to enhance autophagic flux in response to stress.
年龄相关性黄斑变性（AMD）是老年人视力损害的主要原因之一。自噬是将细胞质成分递送至溶酶体进行切割的过程；其与年龄相关的功能障碍可能导致 AMD。在这里，我们表明，OXYS 大鼠中类似 AMD 的视网膜病变的发展伴随着影响自噬相关基因的视网膜转录组变化。这些基因与激酶活性、免疫过程以及 FoxO、mTOR、PI3K-AKT、MAPK、AMPK 和神经营养素途径相关，在临床前和表现阶段，以及在进展阶段与溶酶体中的囊泡运输和过程相关。我们证明了在 16 个月大的 OXYS 视网膜中，自噬调节（抑制或诱导）的反应降低：基因的表达 、 、 、 、 、 和 在 OXYS 和 Wistar（对照）大鼠之间存在差异。根据免疫组织化学分析和透射电子显微镜，在阻断自噬体-溶酶体融合的情况下，自噬体的数量减少，证实了自噬反应的受损。因此，AMD 迹象的发展发生在自噬相关基因表达变化和自噬反应性降低的背景下：即增强对压力的自噬流的能力。
