Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia; Department of Optometry & Vision Sciences, The University of Melbourne, Melbourne, Australia.
Mol Aspects Med. 2023 Aug;92:101193. doi: 10.1016/j.mam.2023.101193. Epub 2023 Jun 16.
Glaucoma is a common, complex, multifactorial neurodegenerative disease characterized by progressive dysfunction and then loss of retinal ganglion cells, the output neurons of the retina. Glaucoma is the most common cause of irreversible blindness and affects ∼80 million people worldwide with many more undiagnosed. The major risk factors for glaucoma are genetics, age, and elevated intraocular pressure. Current strategies only target intraocular pressure management and do not directly target the neurodegenerative processes occurring at the level of the retinal ganglion cell. Despite strategies to manage intraocular pressure, as many as 40% of glaucoma patients progress to blindness in at least one eye during their lifetime. As such, neuroprotective strategies that target the retinal ganglion cell and these neurodegenerative processes directly are of great therapeutic need. This review will cover the recent advances from basic biology to on-going clinical trials for neuroprotection in glaucoma covering degenerative mechanisms, metabolism, insulin signaling, mTOR, axon transport, apoptosis, autophagy, and neuroinflammation. With an increased understanding of both the basic and clinical mechanisms of the disease, we are closer than ever to a neuroprotective strategy for glaucoma.
青光眼是一种常见的、复杂的、多因素的神经退行性疾病，其特征是视网膜神经节细胞（视网膜的输出神经元）进行性功能障碍，随后丧失。青光眼是全球最常见的致盲原因之一，全世界约有 8000 万人受到影响，还有更多的人未被诊断出来。青光眼的主要危险因素是遗传、年龄和眼内压升高。目前的策略仅针对眼内压管理，而不直接针对视网膜神经节细胞水平发生的神经退行性过程。尽管采取了控制眼内压的策略，但多达 40%的青光眼患者在其一生中至少有一只眼睛进展为失明。因此，针对视网膜神经节细胞和这些神经退行性过程的神经保护策略具有巨大的治疗需求。本综述将涵盖从基础生物学到正在进行的青光眼神经保护临床试验的最新进展，涉及退行性机制、代谢、胰岛素信号、mTOR、轴突运输、细胞凋亡、自噬和神经炎症。随着对疾病的基础和临床机制的理解不断加深，我们比以往任何时候都更接近青光眼的神经保护策略。
