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.

Glaucoma is a leading cause of irreversible blindness worldwide and is primarily managed through IOP reduction, though its underlying pathophysiology remains incompletely understood. This study investigates metabolic alterations in glaucoma via targeted metabolomic profiling to identify potential biomarkers and pathogenic mechanisms. Aqueous humor samples were collected from 191 patients at Pauls Stradins Clinical University Hospital immediately before the initiation of cataract surgery, ensuring preoperative conditions. Quantitative metabolite profiling was conducted using liquid chromatography coupled to a Thermo Orbitrap Exploris 120 mass spectrometer. A significant association was observed between open-angle glaucoma and the presence of PEXS (χ²(1) = 9.96, p = 0.002, Cramer's V = 0.228). Several metabolites, including tryptophan, leucine, phenylalanine, and glutamine, were significantly upregulated in glaucoma patients (all p < 0.003, FDR = 0.0358), with tyrosine showing a similar trend (p = 0.0034, FDR = 0.0358). These findings suggest dysregulation of aromatic amino acid metabolism and potential impairment of amino acid hydroxylases, possibly linked to reduced tetrahydrobiopterin (BH4) availability. Disruption in BH4 regeneration-driven by oxidative stress or MTHFR polymorphisms-may impair nitric oxide synthesis and contribute to disease progression. Elevated glutamine and leucine levels could reflect compensatory neuroprotective mechanisms against excitotoxic damage. Our findings suggest that altered biopterin-related cofactor metabolism in aqueous humor may disrupt nitric oxide production and exacerbate oxidative stress, both of which are key factors in glaucoma pathogenesis. These insights highlight the potential of oxidative stress-related biomarkers and antioxidant-based strategies for future glaucoma diagnosis and therapy.

Purpose: To investigate the role of the kynurenine pathway (KP) in ocular diseases by evaluating the activity of key enzymes—kynurenine aminotransferase (KAT) and kynurenine monooxygenase (KMO)—and the 3-hydroxykynurenine to kynurenic acid (3-HK/KYNA) ratio in relation to cataract severity, diabetes, glaucoma, and pseudoexfoliation syndrome (PEXS). Methods: Tryptophan metabolite levels were measured in patients undergoing cataract surgery and stratified by SPONCS grading and comorbid conditions. KAT and KMO activities were estimated using metabolite ratios (KYNA/KYN and 3-HK/KYN, respectively). Statistical analyses included Kruskal–Wallis tests with post hoc comparisons and Mann–Whitney U tests. Results: KAT activity declined significantly with increasing SPONCS grade (p = 0.014), suggesting a progressive loss of KYNA production and antioxidative capacity in advanced cataracts. Diabetic patients exhibited higher KMO activity (p = 0.039) and elevated 3-HK/KYNA ratios (p = 0.013), indicating a metabolic shift toward oxidative stress and neurotoxicity. Similarly, glaucoma patients had significantly increased KMO activity (p = 0.032), consistent with enhanced 3-HK-mediated retinal ganglion cell damage. In contrast, PEXS showed no significant alterations in KP markers. Conclusions: The kynurenine pathway is differentially modulated in ocular diseases. A decline in KAT activity correlates with cataract severity, while upregulation of KMO is prominent in diabetes and glaucoma, revealing disease-specific metabolic dysregulation. Targeting KMO to reduce toxic metabolite accumulation or enhancing KYNA synthesis may offer novel therapeutic avenues. These findings also support the potential of KP metabolites as biomarkers for disease monitoring and progression.

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 X_c⁻ 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 X_c⁻. Treatment of pseudoexfoliation should lower the oxidative stress inside the anterior chamber by reducing the uptake of PUFAs, lower iron levels, and cysteine supplementation.

Purpose: This study evaluates the discrepancies between ACV measurements obtained from the Heidelberg Anterion and Zeiss IOLMaster 700 and investigates the significance of ACV and other ocular biometry parameters. Patients and Methods: To investigate intraocular fluid circulation, a robust formula was developed for ACV measurement using the Zeiss IOLMaster 700. A pilot study was conducted to validate this formula, which relied on WTW, CCT, and ACD. The formula used was ACV = (RAC)^2 × (CCD) × 1.51. ACV measurements showed a median of 155.38 (IQR = 131.15– 180.06) for the Heidelberg Anterion and 144.11 mm³ (IQR = 125.62– 159.81) for the Zeiss IOLMaster 700. The intraclass correlation coefficient (ICC) for ACV was 0.908, indicating excellent agreement between devices. Results: Intraocular fluid volume was significantly lower in eyes with PEXS compared to those without. Eyes with PEX had an ACV of 133 ± 28.3 mm³ versus 142 ± 30.7 mm³ in non-PEX eyes, a statistically significant difference (t (196) = − 2.09, p = 0.038, d = − 0.301). Significant differences were also observed in ACD and AL between PEX and non-PEX eyes, with PEX eyes showing reduced measurements. Conclusion: Our findings reveal that age-related changes in ACD and ACV are significant, with the redefined formula showing excellent agreement with AS-OCT methods. Eyes with PEX exhibit reduced ACD, ACV, and AL measurements. Additionally, an accessible method for ACV measurement, not relying on Pentacam or AS-OCT, would be valuable, particularly in developing countries, to facilitate broader clinical research. Plain Language Summary: Our study examines the differences in measuring aqueous humor volume in the eye using two devices, the Heidelberg Anterion and the Zeiss IOLMaster 700. Aqueous humor is the clear fluid in the front part of the eye, which circulates at a rate of 1.0% to 1.5% per minute. We refined a formula to calculate the volume of this fluid using the Zeiss IOLMaster 700, based on specific eye measurements. We found that the volume measurements from both devices were very similar, showing a strong agreement. The study also discovered that eyes with pseudoexfoliation syndrome (PEXS), a condition affecting the eye, had significantly lower fluid volume compared to eyes without the condition. This was also true for other eye measurements like anterior chamber depth (ACD) and axial length (AL). These findings are important because they show that simpler and more accessible methods for measuring fluid volume in the eye can be used effectively, especially in developing countries where advanced equipment may not be available. The study highlights the changes in eye measurements with age and how the new formula aligns well with existing methods. Overall, eyes with PEX show reduced measurements in various eye parameters.

Cataract is a prevalent, progressive lens disorder characterized by gradual opacity, often related to aging. Oxidative stress, ultraviolet radiation, and inflammation contribute to lens damage and protein modifications. Indoleamine 2,3-dioxygenase plays a critical role in tryptophan metabolism, with kynurenines implicated in various diseases. This study aimed to assess IDO activity in cataract patients by analyzing IDO activity in aqueous humor. The study included 170 cataract surgery patients (60 males, 110 females; mean age 73.9 ± 9.43 years). Cataract severity was categorized using the SPONCS system: SPONCS 1 (1.8%), SPONCS 2 (30.6%), SPONCS 3 (35.3%), SPONCS 4 (11.8%), and SPONCS 5 (20.6%). Aqueous humor samples (50-120 µL) were collected via paracentesis and analyzed using HILIC liquid chromatography with mass spectrometry. Target metabolite quantification was performed using internal standards and calibration curves. Significant differences in IDO activity were observed across SPONCS groups (X²(4) = 12.0, p = .018, Ɛ²= 0.0707), particularly between SPONCS 2 and SPONCS 5 (p = .013). Age differences across SPONCS groups were also significant (p < .001). Males had lower tryptophan levels than females (p = .027). Correlations were found between SPONCS and IDO activity (r_s = -0.255, p < .001), SPONCS and kynurenine (r_s = 0.196, p = .011), and kynurenic acid with kynurenine (r_s = 0.355, p < .001). Patients with SPONCS 2 cataract exhibit increased susceptibility to elevated IDO activity and heightened kynurenine production. IDO serves as a more reliable prognostic marker for cataract progression than chronological age. Furthermore, IDO activity may be associated with reduced glutathione levels in human lens epithelial cells, suggesting a potential link between the enzyme and oxidative stress within the lens.