Metabolomics Reveals Differences in Aqueous Humor Composition in Patients With and Without Pseudoexfoliation Syndrome

Abstract

Pseudoexfoliation syndrome (XFS) is stress- or inflammation-induced elastosis accompanied by excessive production of microfibrils and their deposition in the anterior segment of the eye. Approximately 60–70 million people are affected by XFS worldwide. It is a component of a systemic disorder, considered a major risk factor for accelerated cataract formation, cataract surgery complications and development of glaucoma, which untreated or inadequately treated may lead to blindness. Moreover, XFS has been associated with cardiovascular and cerebrovascular morbidity, dementia, sensorineural hearing loss and pelvic organ prolapse. The pathogenesis of XFS has not been fully elucidated yet. Aqueous humor (AH) is a transparent fluid filling the anterior and posterior chambers of the eye. Determination of AH metabolites that are characteristic for XFS may provide valuable information about the molecular background of this ocular disorder. The aim of this study was to compare the composition of AH in XFS and non-XFS patients undergoing cataract surgery. The AH samples from 34 patients (15 with XFS and 19 without) were analyzed using liquid chromatography coupled to a Quadrupole Time-of-Flight mass spectrometer (LC-QTOF-MS). The obtained metabolic fingerprints were analyzed using multivariate statistics. Eleven statistically significant metabolites were identified. Compared with the non-XFS group, the AH of patients with XFS contained significantly lower levels of amino acids and their derivatives, for example, arginine (−31%, VIP = 2.38) and homo-arginine (−19%, VIP = 1.38). Also, a decrease in the levels of two acylcarnitines, hydroxybutyrylcarnitine (−29%, VIP = 1.24) and decatrienoylcarnitine (−46%, VIP = 1.89), was observed. However, the level of indoleacetaldehyde in XFS patients was significantly higher (+96%, VIP = 2.64). Other significant metabolites were two well-recognized antioxidants, ascorbic acid (−33%, VIP = 2.11) and hydroxyanthranilic acid (−33%, VIP = 2.25), as well as S-adenosylmethionine, a compound with anti-inflammatory properties (−29%, VIP = 1.93). Metabolic pathway analysis demonstrated that the identified metabolites belonged to eight metabolic pathways, with cysteine and methionine metabolism as well as arginine and proline metabolism being the most frequently represented. XFS can be associated with enhanced oxidative stress and inflammation, as well as with the disturbances of cellular respiration and mitochondrial energy production. Implementation of non-targeted metabolomics provided a better insight into the still not fully understood pathogenesis of XFS.

RETRACTED: Comparative study of the ciliary body and iris morphology in the anterior eye chamber of five different vertebrate classes

“…Aqueous humour contains ions, crystalloids, low molecular substances, proteins, lipids, and biologically active substances (Shahidullah et al, 2011). Understanding the regulation, composition and secretion of aqueous humour is an important tool in the treatment and diagnosis of some diseases, such as glaucoma and Pseudoexfoliation Syndrome (Dmuchowska et al, 2021;Shahidullah et al, 2011;Zaidi et al, 2010).…”

Correlation analysis of aqueous humor metabolomics with myopic axial length and choroidal parameters

“…In humans, indoleacetaldehyde is involved in many enzymatic reactions and tryptophan metabolism. Elevated levels of indoleacetaldehyde have been observed in Pseudoexfoliation syndrome (XFS), a disease associated with local stress or the development of inflammation that is usually associated with vasodilation and altered permeability [ 27 ]. Therefore, the level of indoleacetaldehyde also reflects the changes in the intraocular inflammatory microenvironment and vascular status.…”

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.…”