Aberrant protein trafficking in retinal degenerations: The initial phase of retinal remodeling.

Retinal trafficking proteins are involved in molecular assemblies that govern protein transport, orchestrate cellular events involved in cilia formation, regulate signal transduction, autophagy and endocytic trafficking, all of which if not properly controlled initiate retinal degeneration. Improper function and or trafficking of these proteins and molecular networks they are involved in cause a detrimental cascade of neural retinal remodeling due to cell death, resulting as devastating blinding diseases. A universal finding in retinal degenerative diseases is the profound detection of retinal remodeling, occurring as a phased modification of neural retinal function and structure, which begins at the molecular level. Retinal remodeling instigated by aberrant trafficking of proteins encompasses many forms of retinal degenerations, such as the diverse forms of retinitis pigmentosa (RP) and disorders that resemble RP through mutations in the rhodopsin gene, retinal ciliopathies, and some forms of glaucoma and age-related macular degeneration (AMD). As a large majority of genes associated with these different retinopathies are overlapping, it is imperative to understand their underlying molecular mechanisms. This review will discuss some of the most recent discoveries in vertebrate retinal remodeling and retinal degenerations caused by protein mistrafficking.

视网膜运输蛋白参与分子组装，这些分子组装控制蛋白质运输，协调与纤毛形成有关的细胞活动，调节信号转导、自噬和内吞运输，所有这些过程如果得不到适当控制就会引发视网膜变性。这些蛋白质及其所涉及的分子网络功能异常和/或运输不当会因细胞死亡导致神经视网膜重塑的有害级联反应，从而引发严重的致盲疾病。视网膜变性疾病的一个普遍发现是能显著检测到视网膜重塑，它表现为神经视网膜功能和结构的阶段性改变，始于分子水平。由蛋白质异常运输引发的视网膜重塑包含多种形式的视网膜变性，例如多种形式的色素性视网膜炎（RP）以及因视紫红质基因突变而类似RP的疾病、视网膜纤毛病，以及某些形式的青光眼和年龄相关性黄斑变性（AMD）。由于与这些不同视网膜病变相关的大多数基因是重叠的，了解其潜在的分子机制至关重要。本综述将讨论脊椎动物视网膜重塑以及由蛋白质运输错误导致的视网膜变性的一些最新发现。