Metabolomic analysis of aqueous humor reveals potential metabolite biomarkers for differential detection of macular edema

Abstract

Background Macular edema (ME) is a major complication of retinal disease with multiple mechanisms involved in its development. This study aimed to investigate the metabolite profile of aqueous humor (AH) in patients with ME of different etiologies and identify potential metabolite biomarkers for early diagnosis of ME. Methods Samples of AH were collected from 60 patients with ME and 20 age- and sex-matched controls and analyzed by liquid chromatography-mass spectrometry (LC/MS)-based metabolomics. A series of univariate and multivariate statistical analyses were performed to identify differential metabolites and enriched metabolite pathways. Results The metabolic profile of AH differed significantly between ME patients and healthy controls, and differentially expressed metabolites were identified. Pathway analysis revealed that these differentially expressed metabolites are mainly involved in lipid metabolism and amino acid metabolism. Moreover, significant differences were identified in the metabolic composition of AH from patients with ME due to different retinal diseases including age-related macular degeneration (AMD-ME), diabetic retinopathy (DME) and branch retinal vein occlusion (BRVO-ME). In total, 39 and 79 etiology-specific altered metabolites were identified for AMD-ME and DME, respectively. Finally, an AH-derived machine learning-based diagnostic model was developed and successfully validated in the test cohort with an area under the receiver operating characteristic (ROC) curve of 0.79 for AMD-ME, 0.94 for DME and 0.77 for BRVO-ME. Conclusions Our study illustrates the potential underlying metabolic basis of AH of different etiologies across ME populations. We also identify AH-derived metabolite biomarkers that may improve the differential diagnosis and treatment stratification of ME patients with different etiologies.

Recurrence of macular edema in patients with branch retinal vein occlusion: a proteomic study

“…This eventually leads to ME, which carries the risk of blindness or severe vision loss [ 18 ]. The AH plays an important role in maintaining homeostasis in the eyes, and analysis of the AH can provide new insights into our understanding of the pathophysiology of retinal diseases [ 13 ]. This study aimed to analyze the AH protein profiles of patients with BRVO and identify potential biomarkers related to disease pathophysiology.…”

“…Protein levels in the aqueous humor (AH) both anteriorly and posteriorly, are altered in various ocular diseases [ 12 ]. Compared to vitreous fluid and plasma, the convenience and safety of AH collection increases its feasibility for future ophthalmic studies [ 13 ].…”

Retinal Hydration Assessment With Optical Coherence Tomography: Unraveling Its Significance in Retinal Fluid Dynamics, Macular Edema and Cell Viability

“…Additionally, the fluid constituents can be a significant factor in the clinical characteristics of the edema. 23 Understanding the composition of intraretinal fluid may provide valuable insights into the pathophysiology of various macular disorders. Mechanical factors, such as traction forces on the retina resulting from vitreomacular traction or epiretinal membranes, can contribute to developing or exacerbating existing edema, and thus, RH levels.…”

Critical Factors in Sample Collection and Preparation for Clinical Metabolomics of Underexplored Biological Specimens

“…Pure solvents, such as methanol [ 33 , 34 , 35 , 36 ] and acetonitrile [ 29 ], are frequently used in tear extraction after collection via TSs and capillary tubes. For AH and VH extraction, a single protein precipitation step can be applied using cold (below 4 °C) polar organic solvents, such as methanol 75–100% [ 37 , 38 , 39 , 40 ] and mixtures, including acetonitrile/methanol (1:1, v / v ) [ 41 , 42 , 43 , 44 , 45 , 46 ], methanol/ethanol (1:1, v / v ) [ 47 ], and chloroform/methanol (2:1, v / v ) [ 31 , 48 , 49 ], are applied.…”