Browsing by Author "Klavins, Kristaps"

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    Aqueous humor metabolomic profiling identifies a distinct signature in pseudoexfoliation syndrome
    (2024) Zemītis, Artūrs; Vanags, Juris; Schiemer, Theresa; Klavins, Kristaps; Laganovska, Guna; Department of Ophthalmology
    Purpose: PEXS was first described in 1917, yet its etiology still needs clarification. An imbalance between oxidants and antioxidants plays a significant role. PEXS leads to various ocular complications, including increased risk during cataract surgery due to weak zonules, lens dislocation, and reduced visual outcomes. Our study investigates whether metabolomics can provide insights into this ocular pathology. Methods: The study included 183 patients undergoing cataract surgery at Pauls Stradins Clinical University Hospital. 104 patients did not have PEXS, while 79 were diagnosed with the condition. Intraocular fluid samples from these patients were analyzed using targeted metabolite analysis, performed through HILIC liquid chromatography coupled with mass spectrometry detection. Results: The aqueous humor of PEXS patients contains statistically significant higher levels of cystine (p < 0.001), citrulline (p < 0.001), phenylalanine (p = 0.041), tyrosine (p = 0.025), serine (p = 0.030), arginine (p = 0.017), lactic acid (p = 0.055), tryptophan (p = 0.055), and creatinine (p = 0.022). These results suggest a potential link to ferroptosis. Conclusion: Ferroptosis is a form of programmed cell death characterized by iron-dependent LPO. The inhibition of the antiporter system Xc− leads to increased oxidative stress, suggesting that the changes seen in PEXS could be linked to ferroptosis. Our findings indicate that cysteine synthesis occurs via the transsulfation pathway, attributable to inhibiting the antiporter system Xc−. Treatment of pseudoexfoliation should lower the oxidative stress inside the anterior chamber by reducing the uptake of PUFAs, lower iron levels, and cysteine supplementation.
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    Metabolomic Disparities in Intraocular Fluid Across Varied Stages of Cataract Progression : Implications for the Analysis of Cataract Development
    (2024-10-01) Zemitis, Arturs; Vanags, Juris; Fan, Jingzhi; Klavins, Kristaps; Laganovska, Guna; Department of Ophthalmology
    Introduction: The lens's metabolic demands are met through a continuous circulation of aqueous humor, encompassing a spectrum of components such as organic and inorganic ions, carbohydrates, glutathione, urea, amino acids, proteins, oxygen, carbon dioxide, and water. Metabolomics is a pivotal tool, offering an initial insight into the complexities of integrated metabolism. In this investigative study, we systematically scrutinize the composition of intraocular fluid in individuals afflicted with cataracts. Methods: The investigation involved a comprehensive analysis of aqueous humor samples from a cohort comprising 192 patients. These individuals were stratified by utilizing the SPONCS classification system, delineating distinct groups characterized by the hardness of cataracts. The analytical approach employed targeted quantitative metabolite analysis using HILIC-based liquid chromatography coupled with high-resolution mass spectrometric detection. The metabolomics data analysis was performed with MetaboAnalyst 5.0. Results: The results of the enrichment analysis have facilitated the inference that the discerned disparities among groups arise from disruptions in taurine and hypotaurine metabolism, variations in tryptophan metabolism, and modifications in mitochondrial beta-oxidation of short-chain saturated fatty acids and pyrimidine metabolism. Conclusion: A decline in taurine concentration precipitates diminished glutathione activity, prompting an elevated requirement for NAD+ and instigating tryptophan metabolism along the kynurenine pathway. Activation of this pathway is additionally prompted by interferon-gamma and UV radiation, leading to the induction of IDO. Concurrently, heightened mitochondrial beta-oxidation signifies a distinctive scenario in translocating fatty acids into the mitochondria, enhancing energy production.