Metabolomic Profile of Posner–Schlossman Syndrome: A Gas Chromatography Time-of-Flight Mass Spectrometry-Based Approach Using Aqueous Humor

Abstract

The Posner–Schlossman syndrome (PSS) is a disease with clinically recurrent unilateral anterior uveitis with markedly elevated intraocular pressure (IOP) and subsequent progression to optic neuropathy. Retrospective studies have reported increased annual incidence of PSS, especially in China. While currently, the clinical management of PSS is still challenging. Metabolomics is considered to be a sensitive approach for the development of novel targeted therapeutics because of its direct elucidation of pathophysiological mechanisms. Therefore, we adopted gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) technology-based non-targeted metabolomics approach to measure comprehensive metabolic profiles of aqueous humor (AH) samples obtained from patients with PSS, with an aim to demonstrate the underlying pathophysiology, identify potential biomarkers specific to PSS, and develop effective treatment strategies. A comparative analysis was used to indicate the distinct metabolites of PSS. Pathway analysis was conducted using MetaboAnalyst 4.0 to explore the metabolic reprogramming pathways involved in PSS. Logistic regression and receiver-operating characteristic (ROC) analyses were employed to evaluate the diagnostic capability of selected metabolites. Comparative analysis revealed a clear separation between PSS and control groups. Fourteen novel differentiating metabolites from AH samples obtained from patients with PSS were highlighted. Pathway analysis identified 11 carbohydrate, amino acid metabolism and energy metabolism pathways as the major disturbed pathways associated with PSS. The abnormal lysine degradation metabolism, valine–leucine–isoleucine biosynthesis, and citrate circle were considered to weigh the most in the development of PSS. The ROC analysis implied that the combination of glycine and homogentisic acid could serve as potential biomarkers for the discrimination of control and PSS groups. In conclusion, these results revealed for the first time the identity of important metabolites and pathways contributing to the development/progression of PSS, enabled the better understanding of the mechanism of PSS, and might lead to the development of metabolic biomarkers and novel therapeutic strategies to restrict the development/progression of PSS.

Metabolomic Analysis of Aqueous Humor Identifies Aberrant Amino Acid and Fatty Acid Metabolism in Vogt-Koyanagi-Harada and Behcet’s Disease

“…Moreover, alanine was recently found to be essential for early T cell activation and deprivation of it might impair T cell effector functions ( 31 ). Previous metabolic profiling of aqueous humor obtained from acute anterior uveitis and Posner–Schlossman syndrome patients showed differences concerning amino acid metabolism ( 32 , 33 ). Our previous metabolomics study of sweat also revealed an important role for amino acid metabolism in the pathogenesis of VKH disease ( 10 ).…”

“…These operations are not very frequently done and it therefore took us quite some time to collect the desired number of samples from these two well-defined uveitis entities. Most aqueous metabolomics studies in the field of ophthalmology consist of less than 30 samples in each group ( 32 , 33 ). The relatively small sample size might limit the finding of other differentially expressed metabolites.…”

Identification of Urine Metabolic Biomarkers for Vogt-Koyanagi-Harada Disease

“…To the best of our knowledge this is the first study reporting urinary metabolomics in uveitis. Previous studies addressed aqueous humor or plasma as a source for metabolomics analysis Possner Schlossman syndrome and HLA-B27 associated acute anterior uveitis ( Verhagen et al, 2019 ; Wang et al, 2019 ). Although aqueous humor is a biological fluid in direct contact with the site of inflammation it is an invasive procedure and ethical considerations may limit its use.…”

Clinical Characteristics of Virus-related Uveitic Secondary Glaucoma: Focus on Cytomegalovirus and Varicella Zoster Virus

“…Further, we corrected the viral antibody in the aqueous humor using aqueous and serum albumin as follows: (aqueous CMV or VZV IgG/serum CMV or VZV IgG)/ (aqueous albumin concentration/serum albumin concentration). The result was considered positive when viral IgG was detected in aqueous humor and the aqueous humor/serum correction ratio was larger than the optimal threshold calculated by the ROC curve (23,24).…”