Liu Xin, Wu Yue, Liu Yuying, Qian Wenzhe, Huang Liandi, Wu Yixiang, Ke Bilian
Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Shanghai, 200080, China; National Clinical Research Center for Eye Diseases, Shanghai, China; Shanghai Key Laboratory of Fundus Disease, Shanghai, China; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China; Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China.
Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Shanghai, 200080, China; Department of Ophthalmology, Shanghai Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 160 Pujian Road, Shanghai, 200127, China; National Clinical Research Center for Eye Diseases, Shanghai, China; Shanghai Key Laboratory of Fundus Disease, Shanghai, China; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China; Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China.
Exp Eye Res. 2025 Feb;251:110152. doi: 10.1016/j.exer.2024.110152. Epub 2024 Nov 26.
Pathological myopia (PM) is associated with ocular morbidities that cause blindness. PM often occurs in eyes with high myopia (HM) while they are distinctly different. Identifying the differences in metabolites and metabolic pathways between patients with PM and HM may provide information about the pathogenesis of PM, which is currently unknown. This study aimed to reveal the comprehensive metabolic alterations associated with PM. Thirty patients with PM, 27 with simple HM and 27 with low myopia (LM) were enrolled in this study. Ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was performed, and a Venn diagram was generated to explore the overlapping differential metabolites and enriched pathways between each set of two groups. The area under the receiver operating characteristic curve (AUC) was computed to assess the discrimination capacity of each metabolite marker. A total of 134, 125 and 81 differential metabolites were identified in each comparison. Thirty-two differential metabolites were overlapped between the PM vs HM comparison and the PM vs LM comparison. Of these 32 metabolites, 16 were common to all three comparisons; among these metabolites, high levels of 4-hydroxy-l-glutamic acid and low levels of succinic semialdehyde and 2,3-dinor-8-iso prostaglandin F2α appeared to be risk factors for PM. The remaining 16 metabolites were shared only between the PM versus HM and PM versus LM comparisons, most of which are lipid molecules. Pathway analysis revealed that alanine, aspartate and glutamate metabolism was the key metabolic pathway altered in PM patients. Overall, significant differences in the metabolites and metabolic pathways were observed in patients with PM. The metabolic differences identified in this study included differential factors between PM and HM patients, addressing current gaps in PM research. These findings provide a novel perspective of the molecular mechanism of PM.
病理性近视（PM）与导致失明的眼部疾病相关。PM常发生于高度近视（HM）眼中，但其二者明显不同。识别PM患者与HM患者之间代谢物和代谢途径的差异，可能会为目前尚不清楚的PM发病机制提供信息。本研究旨在揭示与PM相关的全面代谢改变。本研究纳入了30例PM患者、27例单纯HM患者和27例低度近视（LM）患者。采用超高效液相色谱/串联质谱法（UPLC-MS/MS）进行检测，并绘制维恩图以探索每组两组之间重叠的差异代谢物和富集途径。计算受试者工作特征曲线（AUC）下的面积，以评估每个代谢物标志物的鉴别能力。在每次比较中分别鉴定出134、125和81种差异代谢物。PM与HM比较和PM与LM比较之间有32种差异代谢物重叠。在这32种代谢物中，有16种在所有三次比较中都相同；在这些代谢物中，4-羟基-L-谷氨酸水平升高以及琥珀酸半醛和2,3-二去甲-8-异前列腺素F2α水平降低似乎是PM的危险因素。其余16种代谢物仅在PM与HM及PM与LM比较之间共有，其中大多数是脂质分子。通路分析显示，丙氨酸、天冬氨酸和谷氨酸代谢是PM患者中改变的关键代谢途径。总体而言，PM患者在代谢物和代谢途径上存在显著差异。本研究中确定的代谢差异包括PM与HM患者之间的差异因素，填补了目前PM研究中的空白。这些发现为PM的分子机制提供了新的视角。
