Arrigo Alessandro, Cremona Ottavio, Aragona Emanuela, Casoni Filippo, Consalez Giacomo, Dogru Rüya Merve, Hauck Stefanie M, Antropoli Alessio, Bianco Lorenzo, Parodi Maurizio Battaglia, Bandello Francesco, Grosche Antje
Ophthalmology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Eye Repair Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Vita-Salute San Raffaele University, Milan, Italy; Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Prog Retin Eye Res. 2025 May;106:101357. doi: 10.1016/j.preteyeres.2025.101357. Epub 2025 Apr 18.
Müller cells are a crucial retinal cell type involved in multiple regulatory processes and functions that are essential for retinal health and functionality. Acting as structural and functional support for retinal neurons and photoreceptors, Müller cells produce growth factors, regulate ion and fluid homeostasis, and facilitate neuronal signaling. They play a pivotal role in retinal morphogenesis and cell differentiation, significantly contributing to macular development. Due to their radial morphology and unique cytoskeletal organization, Müller cells act as optical fibers, efficiently channeling photons directly to the photoreceptors. In response to retinal damage, Müller cells undergo specific gene expression and functional changes that serve as a first line of defense for neurons, but can also lead to unwarranted cell dysfunction, contributing to cell death and neurodegeneration. In some species, Müller cells can reactivate their developmental program, promoting retinal regeneration and plasticity-a remarkable ability that holds promising therapeutic potential if harnessed in mammals. The crucial and multifaceted roles of Müller cells-that we propose to collectively call "Müller cells trophism"-highlight the necessity of maintaining their functionality. Dysfunction of Müller cells, termed "Müller cells pathology," has been associated with a plethora of retinal diseases, including age-related macular degeneration, diabetic retinopathy, vitreomacular disorders, macular telangiectasia, and inherited retinal dystrophies. In this review, we outline how even subtle disruptions in Müller cells trophism can drive the pathological cascade of Müller cells pathology, emphasizing the need for targeted therapies to preserve retinal health and prevent disease progression.
米勒细胞是一种关键的视网膜细胞类型，参与多种对视网膜健康和功能至关重要的调节过程和功能。作为视网膜神经元和光感受器的结构和功能支持，米勒细胞产生生长因子，调节离子和液体稳态，并促进神经元信号传导。它们在视网膜形态发生和细胞分化中起关键作用，对黄斑发育有显著贡献。由于其放射状形态和独特的细胞骨架组织，米勒细胞充当光纤，有效地将光子直接引导至光感受器。响应视网膜损伤时，米勒细胞会经历特定的基因表达和功能变化，这既是神经元的第一道防线，但也可能导致不必要的细胞功能障碍，进而导致细胞死亡和神经退行性变。在某些物种中，米勒细胞可以重新激活其发育程序，促进视网膜再生和可塑性——如果能在哺乳动物中加以利用，这种非凡的能力具有巨大的治疗潜力。我们建议将米勒细胞的这些关键且多方面的作用统称为“米勒细胞营养作用”，这凸显了维持其功能的必要性。米勒细胞功能障碍，即“米勒细胞病变”，与多种视网膜疾病相关，包括年龄相关性黄斑变性、糖尿病性视网膜病变、玻璃体黄斑病变、黄斑毛细血管扩张症和遗传性视网膜营养不良。在本综述中，我们概述了即使是米勒细胞营养作用的细微破坏如何引发米勒细胞病变的病理级联反应，强调了需要有针对性的治疗来维护视网膜健康并预防疾病进展。
