Pinelli Roberto, Lazzeri Gloria, Berti Caterina, Biagioni Francesca, Scaffidi Elena, Ferrucci Michela, Bumah Violet Vakunseh, Fornai Francesco
SERI, Switzerland Eye Research Institute, 6900 Lugano, Switzerland.
Human Anatomy, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, PI, Italy.
Int J Mol Sci. 2025 Jun 16;26(12):5773. doi: 10.3390/ijms26125773.
Current evidence indicates that most types of autophagy represent a pivot in promoting retinal integrity. In healthy conditions, autophagy acts on multiple pathways, which are fundamental for the biochemistry and the fine structure of the retina. Autophagy is essential in granting visual processes. On the other hand, autophagy dysfunction characterizes several retinal disorders. This is mostly evident in age-related macular degeneration (AMD), which represents the most common degenerative disease leading to blindness. The involvement of autophagy in AMD is documented in vitro and in vivo experiments, and it is strongly suggested by clinical findings in humans. The present manuscript provides an overview of the specific types of autophagy, which prevail in the retina and their alterations in retinal degeneration with an emphasis on AMD. The dysfunction of specific autophagy steps was analyzed in relation to hallmarks of AMD pathology and symptoms. An extended session of the manuscript analyzes the connection between altered autophagy and cell pathology within retinal pigment epithelium, as well as the site and structure of extracellular aggregates named drusen. The significance of the drusen in relation to visual function is discussed in the light of the role of autophagy in regulating key steps of phototransduction.
目前的证据表明，大多数类型的自噬是促进视网膜完整性的关键因素。在健康状态下，自噬作用于多种途径，这些途径对于视网膜的生物化学和精细结构至关重要。自噬对于视觉过程必不可少。另一方面，自噬功能障碍是几种视网膜疾病的特征。这在年龄相关性黄斑变性（AMD）中最为明显，AMD是导致失明的最常见退行性疾病。自噬在AMD中的作用已在体外和体内实验中得到证实，并且在人类临床研究结果中也得到了有力的提示。本手稿概述了在视网膜中占主导地位的自噬的特定类型及其在视网膜变性（尤其是AMD）中的变化。分析了特定自噬步骤的功能障碍与AMD病理学特征和症状之间的关系。手稿的扩展部分分析了自噬改变与视网膜色素上皮细胞病理学之间的联系，以及称为玻璃膜疣的细胞外聚集体的部位和结构。根据自噬在调节光转导关键步骤中的作用，讨论了玻璃膜疣与视觉功能的关系。
