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To investigate the plasma lipoprotein subclasses in patients with primary open-angle glaucoma (POAG), a total of 20 Chinese POAG patients on intraocular pressure (IOP)-lowering treatment and 20 age-matched control subjects were recruited. Based on the levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), the study subjects were divided into elevated- and normal-level subgroups. The plasma lipoprotein, lipoprotein subclasses, and oxidized LDL (oxLDL) levels were quantitatively measured. The discrimination potential of the lipoproteins was evaluated using the area under the receiver operating characteristic curve (AUC), and their correlation with clinical parameters was also evaluated. Compared to the control subjects with elevated TC and/or LDL-C levels, the levels of TC, LDL-C, non-high-density lipoprotein cholesterol (non-HDL), LDL subclass LDL3 and small dense LDL (sdLDL), and oxLDL were significantly higher in POAG patients with elevated TC and/or LDL-C levels. No differences in any lipoproteins or the subclasses were found between the POAG patients and control subjects with normal TC and LDL-C levels. Moderate-to-good performance of TC, LDL-C, non-HDL, LDL3, sdLDL, and oxLDL was found in discriminating between the POAG patients and control subjects with elevated TC and/or LDL-C levels (AUC: 0.710-0.950). Significant negative correlations between LDL3 and sdLDL with retinal nerve fiber layer (RNFL) thickness in the superior quadrant and between LDL3 and average RNFL thickness were observed in POAG patients with elevated TC and/or LDL-C levels. This study revealed a significant elevation of plasma lipoproteins, especially the LDL subclasses, in POAG patients with elevated TC and/or LDL-C levels, providing insights on monitoring specific lipoproteins in POAG patients with elevated TC and/or LDL-C.
Asunto(s)
Glaucoma de Ángulo Abierto , Humanos , Glaucoma de Ángulo Abierto/sangre , Glaucoma de Ángulo Abierto/clasificación , Masculino , Femenino , Persona de Mediana Edad , Anciano , Lipoproteínas LDL/sangre , Lipoproteínas/sangre , Lipoproteínas/clasificación , Presión Intraocular , LDL-Colesterol/sangre , Estudios de Casos y Controles , China , Pueblo Asiatico , Colesterol/sangre , Pueblos del Este de AsiaRESUMEN
OBJECTIVE: To assess the diagnostic ability of peripapillary vessel density (pVD) in primary open-angle glaucoma suspect (GS) patients. METHODS: Sixteen primary open-angle GS patients (22 eyes) and 20 normal controls (22 eyes) were included. In the GS group, OCTA measurements of pVD (superior, inferior, nasal, temporal, and global), OCT measurements of retinal nerve fiber layer (RNFL) thickness, disc area, rim area and ganglion cell complex (GCC) thickness were examined. In the control group, pVD measurements were performed. The vessel density between the two groups was compared. The correlation between OCTA and OCT parameters was evaluated. The receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of OCTA measurements. RESULTS: The global (P < 0.001), nasal (P = 0.003), and inferior (P = 0.002) quadrant pVD in GS group was considerably lower than the control group. The global pVD was positively correlated with the inferior RNFL thickness (r = 0.492, P = 0.023) and rim area (r = 0.483, P = 0.027). The inferior pVD was positively correlated with the inferior RNFL thickness (r = 0.648, P = 0.001), the nasal RNFL thickness (r = 0.441, P = 0.045), the rim area (r = 0.439, P = 0.046) and the GCC thickness (r = 0.472, P = 0.048). The global pVD had the best diagnostic value (AUC=0.825, sensitivity 86.36 %, specificity 72.73 %, cutoff value 45 %), followed by the inferior (AUC=0.749) and nasal (AUC=0.748) quadrant pVD. CONCLUSION: In primary open-angle GS patients, the global and inferior quadrant pVD was lower than that of normal people, and it was positively correlated with the inferior RNFL thickness and rim area. The diagnostic value of pVD for discriminating GS from normal people was excellent with high sensitivity and specificity.
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Purpose: to determine the metabolomics profiles in the plasma samples of primary open-angle glaucoma (POAG) patients. Methods: The plasma samples from 20 POAG patients under intraocular pressure (IOP)-lowering medication treatment and 20 control subjects were subjected to the untargeted metabolomics analysis, among which 10 POAG patients and 10 control subjects were further subjected to the oxylipin-targeted metabolomics analysis by liquid chromatography-mass spectrometry analysis. The prediction accuracy of the differentially abundant metabolites was assessed by the receiver operating characteristic curves. Pathway analysis and correlation analysis on the differentially abundant metabolites and clinical and biochemical parameters were also conducted. Results: Untargeted metabolomics profiling identified 33 differentially abundant metabolites in the POAG patients, in which the metabolism of linoleic acid, α-linolenic acid, phenylalanine, and tricarboxylic acid cycle were enriched. The correlation analysis indicated that the differentially abundant metabolites were associated with central corneal thickness, peripapillary retinal nerve fiber layer thickness, visual field defects, and lymphocytes. The oxylipin-targeted metabolomics analysis identified 15-keto-Prostaglandin F2 alpha, 13,14-Dihydro-15-keto-prostaglandin D2, 11-Dehydro-thromboxane B2, 8,9-Epoxyeicosatrienoic acid, and arachidonic acid to be significantly decreased in the POAG patients and enriched in the arachidonic acid (AA) pathway. Conclusions: This study revealed that the metabolites in the arachidonic acid metabolism pathway are differentially abundant, suggesting high IOP may not be the only detrimental factor for optic nerve cell damage in this group of POAG patients. Lipid metabolism instability-mediated alterations in oxylipins and AA pathways may be important in POAG, suggesting that oxidative stress and immune-related inflammation could be valuable directions for future therapeutic strategies.
Asunto(s)
Glaucoma de Ángulo Abierto , Humanos , Oxilipinas , Ácido Araquidónico , Retina , Presión IntraocularRESUMEN
Deep neural network-based programs can be applied to protein structure modeling by inputting amino acid sequences. Here, we aimed to evaluate the AlphaFold2-modeled myocilin wild-type and variant protein structures and compare to the experimentally determined protein structures. Molecular dynamic and ligand binding properties of the experimentally determined and AlphaFold2-modeled protein structures were also analyzed. AlphaFold2-modeled myocilin variant protein structures showed high similarities in overall structure to the experimentally determined mutant protein structures, but the orientations and geometries of amino acid side chains were slightly different. The olfactomedin-like domain of the modeled missense variant protein structures showed fewer folding changes than the nonsense variant when compared to the predicted wild-type protein structure. Differences were also observed in molecular dynamics and ligand binding sites between the AlphaFold2-modeled and experimentally determined structures as well as between the wild-type and variant structures. In summary, the folding of the AlphaFold2-modeled MYOC variant protein structures could be similar to that determined by the experiments but with differences in amino acid side chain orientations and geometries. Careful comparisons with experimentally determined structures are needed before the applications of the in silico modeled variant protein structures.