PDF(Pubmed)
Abstract：
Glaucoma is the leading cause of irreversible blindness. Current treatment options are limited and often only slow disease progression. Metabolic dysfunction has recently been recognized as a key early and persistent mechanism in glaucoma pathophysiology. Several intrinsic metabolic dysfunctions have been identified and treated in retinal ganglion cells to provide neuroprotection. Growing pre-clinical and clinical evidence has confirmed that metabolic alterations in glaucoma are widespread, occurring across visual system tissues, in ocular fluids, in blood/serum, and at the level of genomic and mitochondrial DNA. This suggests that metabolic dysfunction is not constrained to retinal ganglion cells and that metabolic alterations extrinsic to retinal ganglion cells may contribute to their metabolic compromise. Retinal ganglion cells are reliant on glial metabolic support under normal physiological conditions, but the implications of metabolic dysfunction in glia are underexplored. We highlight emerging evidence that has demonstrated metabolic alterations occurring within glia in glaucoma, and how this may affect neuro-glial metabolic coupling and the metabolic vulnerability of retinal ganglion cells. In other neurodegenerative diseases which share features with glaucoma, several other glial metabolic alterations have been identified, suggesting that similar mechanisms and therapeutic targets may exist in glaucoma.
摘要：
青光眼是不可逆失明的主要原因。目前的治疗选择是有限的，通常只能减缓疾病进展。最近，代谢功能障碍已被认为是青光眼病理生理学中的关键早期和持续机制。已经在视网膜神经节细胞中鉴定并治疗了几种固有的代谢功能障碍以提供神经保护。越来越多的临床前和临床证据已经证实青光眼的代谢改变是广泛的，发生在视觉系统组织中，在眼内液中，在血液/血清中，以及基因组和线粒体DNA的水平。这表明代谢功能障碍不限于视网膜神经节细胞，并且视网膜神经节细胞的外在代谢改变可能导致其代谢受损。视网膜神经节细胞在正常生理条件下依赖于神经胶质代谢支持,但是神经胶质细胞代谢功能障碍的影响还未得到充分研究。我们强调了新出现的证据，表明青光眼神经胶质细胞内发生代谢改变，以及这可能如何影响神经胶质代谢偶联和视网膜神经节细胞的代谢脆弱性。在其他与青光眼具有共同特征的神经退行性疾病中，其他几种神经胶质代谢改变已被确认，提示青光眼可能存在相似的机制和治疗靶点。
