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13 pages, 501 KiB

Open AccessArticle

Tear Fluid Biomarkers and Quality of Life in People with Type 2 Diabetes and Dry Eye Disease

by Mungunshur Byambajav, Andrew Collier, Xinhua Shu and Suzanne Hagan

Metabolites 2023, 13(6), 733; https://doi.org/10.3390/metabo13060733 - 8 Jun 2023

Cited by 3 | Viewed by 2169

Abstract

Dry eye disease (DED) can be extremely distressing and is common in type 2 diabetes (T2D). To investigate potential biomarkers of DED in T2D, panels of proteins in tears, alongside clinical signs and symptoms of DED, were assessed. Patients were classified into four [...] Read more.

Dry eye disease (DED) can be extremely distressing and is common in type 2 diabetes (T2D). To investigate potential biomarkers of DED in T2D, panels of proteins in tears, alongside clinical signs and symptoms of DED, were assessed. Patients were classified into four groups: T2D + DED (n = 47), T2D-only (n = 41), DED-only (n = 17) and healthy controls (n = 17). All patients underwent the Ocular Surface Disease Index (OSDI) and Dry Eye-Related Quality of Life (DEQS) questionnaires, tear evaporation rate (TER), fluorescein tear break-up time (fTBUT), corneal fluorescein staining (CFS) and Schirmer 1 test assessments. Six metabolic proteins and 14 inflammatory cytokines were analyzed with multiplex bead analysis. Interleukin (IL)-6 and IL-8 concentrations in tears were significantly higher in the T2D + DED group, and these biomarkers were positively correlated with CFS. In addition, tear IL-6 was negatively correlated with fTBUT in the T2D + DED group. Clinical signs of DED in the T2D + DED group were similar to the DED-only group. The T2D + DED group had more patients with moderate and severe DED (versus the DED-only group), suggesting a different pathogenesis for DED in T2D versus DED-only. Therefore, IL-6 and IL-8 could potentially be diagnostic biomarkers of DED in T2D. Full article

(This article belongs to the Special Issue Metabolic Studies in Ophthalmology and Visual Science)

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16 pages, 2398 KiB

Open AccessArticle

Machine Learning-Based Integration of Metabolomics Characterisation Predicts Progression of Myopic Retinopathy in Children and Adolescents

by Xiao-Wen Hou, Jin-Liu-Xing Yang, Dan-Lin Li, Yi-Jin Tao, Chao-Fu Ke, Bo Zhang, Shang Liu, Tian-Yu Cheng, Tian-Xiao Wang, Xun Xu, Xian-Gui He and Chen-Wei Pan

Metabolites 2023, 13(2), 301; https://doi.org/10.3390/metabo13020301 - 17 Feb 2023

Cited by 7 | Viewed by 2146

Abstract

Myopic retinopathy is an important cause of irreversible vision loss and blindness. As metabolomics has recently been successfully applied in myopia research, this study sought to characterize the serum metabolic profile of myopic retinopathy in children and adolescents (4–18 years) and to develop [...] Read more.

Myopic retinopathy is an important cause of irreversible vision loss and blindness. As metabolomics has recently been successfully applied in myopia research, this study sought to characterize the serum metabolic profile of myopic retinopathy in children and adolescents (4–18 years) and to develop a diagnostic model that combines clinical and metabolic features. We selected clinical and serum metabolic data from children and adolescents at different time points as the training set (n = 516) and the validation set (n = 60). All participants underwent an ophthalmologic examination. Untargeted metabolomics analysis of serum was performed. Three machine learning (ML) models were trained by combining metabolic features and conventional clinical factors that were screened for significance in discrimination. The better-performing model was validated in an independent point-in-time cohort and risk nomograms were developed. Retinopathy was present in 34.2% of participants (n = 185) in the training set, including 109 (28.61%) with mild to moderate myopia. A total of 27 metabolites showed significant variation between groups. After combining Lasso and random forest (RF), 12 modelled metabolites (mainly those involved in energy metabolism) were screened. Both the logistic regression and extreme Gradient Boosting (XGBoost) algorithms showed good discriminatory ability. In the time-validation cohort, logistic regression (AUC 0.842, 95% CI 0.724–0.96) and XGBoost (AUC 0.897, 95% CI 0.807–0.986) also showed good prediction accuracy and had well-fitted calibration curves. Three clinical characteristic coefficients remained significant in the multivariate joint model (p < 0.05), as did 8/12 metabolic characteristic coefficients. Myopic retinopathy may have abnormal energy metabolism. Machine learning models based on metabolic profiles and clinical data demonstrate good predictive performance and facilitate the development of individual interventions for myopia in children and adolescents. Full article

(This article belongs to the Special Issue Metabolic Studies in Ophthalmology and Visual Science)

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14 pages, 2280 KiB

Open AccessArticle

Integrated Metabolomics and Transcriptomics Reveal Metabolic Patterns in Retina of STZ-Induced Diabetic Retinopathy Mouse Model

by Ruonan Wang, Qizhi Jian, Guangyi Hu, Rui Du, Xun Xu and Fang Zhang

Metabolites 2022, 12(12), 1245; https://doi.org/10.3390/metabo12121245 - 9 Dec 2022

Cited by 11 | Viewed by 2180

Abstract

Diabetic retinopathy (DR), as the leading cause of vision loss in the working-age population, exhibits unique metabolite profiles in human plasma and vitreous. However, those in retina are not fully understood. Here, we utilized liquid and gas chromatography–tandem mass spectrometry technology to explore [...] Read more.

Diabetic retinopathy (DR), as the leading cause of vision loss in the working-age population, exhibits unique metabolite profiles in human plasma and vitreous. However, those in retina are not fully understood. Here, we utilized liquid and gas chromatography–tandem mass spectrometry technology to explore metabolite characteristics of streptozotocin (STZ)-induced diabetic mice retina. A total of 145 metabolites differed significantly in diabetic retinas compared with controls. These metabolites are mainly enriched in the Warburg effect, and valine, leucine and isoleucine degradation pathways. To further identify underlying regulators, RNA sequencing was performed to integrate metabolic enzyme alterations with metabolomics in STZ-induced diabetic retina. Retinol metabolism and tryptophan metabolism are the shared pathways enriched by metabolome and transcriptome. Additionally, transcriptomic analysis identified 71 differentially expressed enzyme-related genes including Hk2, Slc7a5, Aldh1a3 and Tph integrated with altered metabolic pathways. In addition, single nucleotide polymorphisms within 6 out of 71 genes are associated with increased diabetes risk. This study lays the foundation for mechanism research and the therapeutic target development of DR. Full article

(This article belongs to the Special Issue Metabolic Studies in Ophthalmology and Visual Science)

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14 pages, 10683 KiB

Open AccessCommunication

Multiomic Mass Spectrometry Imaging to Advance Future Pathological Understanding of Ocular Disease

by Joshua Millar, Ema Ozaki, Susan Campbell, Catherine Duckett, Sarah Doyle and Laura M. Cole

Metabolites 2022, 12(12), 1239; https://doi.org/10.3390/metabo12121239 - 9 Dec 2022

Cited by 2 | Viewed by 2107

Abstract

Determining the locations of proteins within the eye thought to be involved in ocular pathogenesis is important to determine how best to target them for therapeutic benefits. However, immunohistochemistry is limited by the availability and specificity of antibodies. Additionally, the perceived role of [...] Read more.

Determining the locations of proteins within the eye thought to be involved in ocular pathogenesis is important to determine how best to target them for therapeutic benefits. However, immunohistochemistry is limited by the availability and specificity of antibodies. Additionally, the perceived role of both essential and non-essential metals within ocular tissue has been at the forefront of age-related macular degeneration (AMD) pathology for decades, yet even key metals such as copper and zinc have yet to have their roles deconvoluted. Here, mass spectrometry imaging (MSI) is employed to identify and spatially characterize both proteomic and metallomic species within ocular tissue to advance the application of a multiomic imaging methodology for the investigation of ocular diseases. Full article

(This article belongs to the Special Issue Metabolic Studies in Ophthalmology and Visual Science)

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17 pages, 1437 KiB

Open AccessArticle

First Evidence Indicates the Physiology- and Axial-Myopia-Dependent Profiles of Steroid Hormones in Aqueous Humor

by Tiansheng Chou, Xiaosheng Huang, Jiawei Liu, Xinhua Liu, Kun Zeng, Zonghui Yan, Shaoyi Mei, Liangnan Sun, Wenqun Xi, Jinglan Ni, Jin Zi, Jun Zhao and Siqi Liu

Metabolites 2022, 12(12), 1220; https://doi.org/10.3390/metabo12121220 - 5 Dec 2022

Cited by 2 | Viewed by 1758

Abstract

The quantitative level of steroid hormones (SHs) in some body fluids have been accepted for clinical diagnosis, whereas their distribution in aqueous humor (AH) is unknown yet. Herein, a profiling study was conducted with a total of 171 AH and 107 plasma samples [...] Read more.

The quantitative level of steroid hormones (SHs) in some body fluids have been accepted for clinical diagnosis, whereas their distribution in aqueous humor (AH) is unknown yet. Herein, a profiling study was conducted with a total of 171 AH and 107 plasma samples using liquid chromatography coupled with tandem mass spectrometry (LC MS/MS). For the first time, six kinds of SHs in AH were quantitatively estimated, and their abundances were ranked at cortisol (F), corticosterone (COR), androstenedione (A2), and 11-deoxycortisol (11DOC). The corresponding abundance of all SHs in AH was significantly lower than those in plasma, while there was a lack of a proportional relationship with the abundance of plasma SHs. Dehydroepiandrosterone sulfate, the most abundant plasma SH, was undetectable in AH, implying that the blood–aqueous barrier might specifically block its transferral. Axial myopia generally results from many factors throughout the entire eye from tissues and molecules; furthermore, the correlation of AH SHs and axial myopia was assessed to look for their indication in such myopia. The panel with five kinds of AH SHs (F, COR, CORT, ALD and A2) was functional as a discriminator for axial myopia and control. The abundance of SHs, therefore, has a specific distribution in AH and can potentially contribute to axial myopia. Full article

(This article belongs to the Special Issue Metabolic Studies in Ophthalmology and Visual Science)

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16 pages, 2994 KiB

Open AccessArticle

Metabolomic Study of a Rat Model of Retinal Detachment

by Xiangjun She, Yifan Zhou, Zhi Liang, Jin Wei, Bintao Xie, Yun Zhang and Lijun Shen

Metabolites 2022, 12(11), 1077; https://doi.org/10.3390/metabo12111077 - 7 Nov 2022

Cited by 4 | Viewed by 1943

Abstract

Retinal detachment is a serious ocular disease leading to photoreceptor degeneration and vision loss. However, the mechanism of photoreceptor degeneration remains unclear. The aim of this study was to investigate the altered metabolism pathway and physiological changes after retinal detachment. Eight-week-old male SD [...] Read more.

Retinal detachment is a serious ocular disease leading to photoreceptor degeneration and vision loss. However, the mechanism of photoreceptor degeneration remains unclear. The aim of this study was to investigate the altered metabolism pathway and physiological changes after retinal detachment. Eight-week-old male SD rats were fed, and the model of retinal detachment was established by injecting hyaluronic acid into the retinal space. The rats were euthanized 3 days after RD, and the retinal tissues were sectioned for analysis. Untargeted lipid chromatography-mass spectrometry lipidomic was performed to analyze the metabolite changes. A total of 90 significant metabolites (34 in anionic and 56 in cationic models) were detected after retinal detachment. The main pathways were (1) histidine metabolism; (2) phenylalanine, tyrosine, and tryptophan biosynthesis; and (3) glycine, serine, and threonine metabolism. The key genes corresponding to each metabolic pathway were verified from the Gene Expression Omnibus (GEO) database of human retinal samples. The results indicated that the production of histamine by histidine decarboxylase from histidine reduced after RD (p < 0.05). Xanthine, hypoxanthine, guanine, and guanosine decreased after RD (p < 0.05). Decreased xanthine and hypoxanthine may reduce the antioxidant ability. The decreased guanosine could not provide enough sources for inosine monophosphate production. Tyrosine is an important neurotransmitter and was significantly reduced after RD (p < 0.05). Citrate was significantly reduced with the increase of ATP-citrate lyase enzyme (ACLY) (p < 0.05). We inferred that lipid oxidation might increase rather than lipid biogenesis. Thus, this study highlighted the main changes of metabolite and physiological process after RD. The results may provide important information for photoreceptor degeneration. Full article

(This article belongs to the Special Issue Metabolic Studies in Ophthalmology and Visual Science)

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Review

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17 pages, 894 KiB

Open AccessReview

Metabolomics in Corneal Diseases: A Narrative Review from Clinical Aspects

by Alvin Wei Jun Teo, Jingwen Zhang, Lei Zhou and Yu-Chi Liu

Metabolites 2023, 13(3), 380; https://doi.org/10.3390/metabo13030380 - 3 Mar 2023

Cited by 5 | Viewed by 2389

Abstract

Corneal pathologies may have subtle manifestations in the initial stages, delaying diagnosis and timely treatment. This can lead to irreversible visual loss. Metabolomics is a rapidly developing field that allows the study of metabolites in a system, providing a complementary tool in the [...] Read more.

Corneal pathologies may have subtle manifestations in the initial stages, delaying diagnosis and timely treatment. This can lead to irreversible visual loss. Metabolomics is a rapidly developing field that allows the study of metabolites in a system, providing a complementary tool in the early diagnosis and management of corneal diseases. Early identification of biomarkers is key to prevent disease progression. The advancement of nuclear magnetic resonance and mass spectrometry allows the identification of new biomarkers in the analysis of tear, cornea, and aqueous humor. Novel perspectives on disease mechanisms are identified, which provide vital information for potential targeted therapies in the future. Current treatments are analyzed at a molecular level to offer further information regarding their efficacy. In this article, we provide a comprehensive review of the metabolomic studies undertaken in the cornea and various pathologies such as dry eye disease, Sjogren’s syndrome, keratoconus, post-refractive surgery, contact lens wearers, and diabetic corneas. Lastly, we discuss the exciting future that metabolomics plays in cornea research. Full article

(This article belongs to the Special Issue Metabolic Studies in Ophthalmology and Visual Science)

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19 pages, 1895 KiB

Open AccessReview

Amino Acids Metabolism in Retinopathy: From Clinical and Basic Research Perspective

by Mengxue Xia and Fang Zhang

Metabolites 2022, 12(12), 1244; https://doi.org/10.3390/metabo12121244 - 9 Dec 2022

Cited by 18 | Viewed by 2215

Abstract

Retinopathy, including age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinopathy of prematurity (ROP), are the leading cause of blindness among seniors, working-age populations, and children. However, the pathophysiology of retinopathy remains unclear. Accumulating studies demonstrate that amino acid metabolism is associated with [...] Read more.

Retinopathy, including age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinopathy of prematurity (ROP), are the leading cause of blindness among seniors, working-age populations, and children. However, the pathophysiology of retinopathy remains unclear. Accumulating studies demonstrate that amino acid metabolism is associated with retinopathy. This study discusses the characterization of amino acids in DR, AMD, and ROP by metabolomics from clinical and basic research perspectives. The features of amino acids in retinopathy were summarized using a comparative approach based on existing high-throughput metabolomics studies from PubMed. Besides taking up a large proportion, amino acids appear in both human and animal, intraocular and peripheral samples. Among them, some metabolites differ significantly in all three types of retinopathy, including glutamine, glutamate, alanine, and others. Studies on the mechanisms behind retinal cell death caused by glutamate accumulation are on the verge of making some progress. To develop potential therapeutics, it is imperative to understand amino acid-induced retinal functional alterations and the underlying mechanisms. This review delineates the significance of amino acid metabolism in retinopathy and provides possible direction to discover therapeutic targets for retinopathy. Full article

(This article belongs to the Special Issue Metabolic Studies in Ophthalmology and Visual Science)

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19 pages, 932 KiB

Open AccessReview

Metabolomics and Biomarkers in Retinal and Choroidal Vascular Diseases

by Xiao-Wen Hou, Ying Wang, Chao-Fu Ke, Mei-Yan Li and Chen-Wei Pan

Metabolites 2022, 12(9), 814; https://doi.org/10.3390/metabo12090814 - 30 Aug 2022

Cited by 6 | Viewed by 2250

Abstract

The retina is one of the most important structures in the eye, and the vascular health of the retina and choroid is critical to visual function. Metabolomics provides an analytical approach to endogenous small molecule metabolites in organisms, summarizes the results of “gene-environment [...] Read more.

The retina is one of the most important structures in the eye, and the vascular health of the retina and choroid is critical to visual function. Metabolomics provides an analytical approach to endogenous small molecule metabolites in organisms, summarizes the results of “gene-environment interactions”, and is an ideal analytical tool to obtain “biomarkers” related to disease information. This study discusses the metabolic changes in neovascular diseases involving the retina and discusses the progress of the study from the perspective of metabolomics design and analysis. This study advocates a comparative strategy based on existing studies, which encompasses optimization of the performance of newly identified biomarkers and the consideration of the basis of existing studies, which facilitates quality control of newly discovered biomarkers and is recommended as an additional reference strategy for new biomarker discovery. Finally, by describing the metabolic mechanisms of retinal and choroidal neovascularization, based on the results of existing studies, this study provides potential opportunities to find new therapeutic approaches. Full article

(This article belongs to the Special Issue Metabolic Studies in Ophthalmology and Visual Science)

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