Zhu Wenqing, Guo Linying, Chen Wenwen, Liu Tingting, Sun Xinghuai
Department of Ophthalmology and Visual Science, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Key Laboratory of Myopia and Related Eye Diseases, NHC, Fudan University, Shanghai, China.
Front Cell Dev Biol. 2025 Jun 27;13:1590460. doi: 10.3389/fcell.2025.1590460. eCollection 2025.
Glaucoma, a leading cause of irreversible blindness worldwide, imposes a devastating burden on over 11 million end-stage patients through permanent vision loss. Despite this profound disability, the neurochemical basis of preserved cortical plasticity remains unclear, compounded by the challenge of recruiting this vulnerable population for advanced neuroimaging studies.
We conducted single-voxel proton magnetic resonance spectroscopy (1H-MRS) in 11 blind patients with end-stage primary open-angle glaucoma (POAG) and 11 normal controls to characterize metabolic alterations in the primary visual cortex (V1) and their relationship to residual retinal function.
Glutamate-glutamine complex (Glx), N-acetylaspartate (NAA), choline (Cho), and myo-inositol (Ins) ratios relative to creatine (Cr) were quantified, revealing significantly elevated Glx/Cr in POAG (95% CI: 0.09 ∼ 0.63, P = 0.011), while NAA/Cr, Cho/Cr, and Ins/Cr remained stable (P > 0.05). Notably, the Glx/Cr ratio correlated significantly with the N1-wave latency of mfERG (ρ = -0.676, P = 0.022), independent of other clinical parameters.
These findings demonstrate glutamate hyperactivity coexisting with preserved neuronal and osmotic homeostasis in the V1 of end-stage POAG patients, suggesting adaptive neuroglial compensation. The correlation between Glx/Cr ratios and mfERG responses indicates persistent retinocortical signaling despite blindness, highlighting the potential of 1H-MRS as a valuable tool for assessing cortical plasticity in advanced glaucoma rehabilitation.
青光眼是全球不可逆失明的主要原因，通过永久性视力丧失给超过1100万终末期患者带来了毁灭性负担。尽管存在这种严重的残疾，但保留的皮质可塑性的神经化学基础仍不清楚，招募这一脆弱人群进行高级神经影像学研究也面临挑战。
我们对11例终末期原发性开角型青光眼（POAG）盲患者和11例正常对照进行了单体素质子磁共振波谱（1H-MRS）检查，以表征初级视觉皮层（V1）的代谢改变及其与残余视网膜功能的关系。
对相对于肌酸（Cr）的谷氨酸-谷氨酰胺复合物（Glx）、N-乙酰天门冬氨酸（NAA）、胆碱（Cho）和肌醇（Ins）比率进行了量化，结果显示POAG患者的Glx/Cr显著升高（95%CI：0.09～0.63，P = 0.011），而NAA/Cr、Cho/Cr和Ins/Cr保持稳定（P > 0.05）。值得注意的是，Glx/Cr比率与mfERG的N1波潜伏期显著相关（ρ = -0.676，P = 0.022），独立于其他临床参数。
这些发现表明，终末期POAG患者的V1中谷氨酸活性亢进与神经元和渗透压稳态的保留并存，提示适应性神经胶质细胞补偿。Glx/Cr比率与mfERG反应之间的相关性表明，尽管失明，但视网膜皮质信号持续存在，突出了1H-MRS作为评估晚期青光眼康复中皮质可塑性的有价值工具的潜力。
