Haiyan Wang1, Junwei Fang2, Fenge Chen1, Qian Sun1, Xiaoyin Xu1, Shu-Hai Lin3,4, Kun Liu5. 1. Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China. 2. College of Basic Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 3. College of Basic Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China. shuhai@xmu.edu.cn. 4. State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, China. shuhai@xmu.edu.cn. 5. Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China. drliukun@sjtu.edu.cn.
Abstract
AIM: To identify the potential metabolite markers in diabetic retinopathy (DR) by using gas chromatography coupled with time-of-flight mass spectrometry (GC-TOFMS). METHODS: GC-TOFMS spectra were acquired from vitreous and aqueous humor (AH) samples of patients with DR and non-diabetic participants. Comparative analysis was used to elucidate the distinct metabolites of DR. Metabolic pathway was employed to explicate the metabolic reprogramming pathways involved in DR. Logistic regression and receiver-operating characteristic analyses were carried out to select and validate the biomarker metabolites and establish a therapeutic model. RESULTS: Comparative analysis showed a clear separation between disease and control groups. Eight differentiating metabolites from AH and 15 differentiating metabolites from vitreous were highlighted. Out of these 23 metabolites, 11 novel metabolites have not been detected previously. Pathway analysis identified nine pathways (three in AH and six in vitreous) as the major disturbed pathways associated with DR. The abnormal of gluconeogenesis, ascorbate-aldarate metabolism, valine-leucine-isoleucine biosynthesis, and arginine-proline metabolism might weigh the most in the development of DR. The AUC of the logistic regression model established by D-2,3-Dihydroxypropanoic acid, isocitric acid, fructose 6-phosphate, and L-Lactic acid in AH was 0.965. The AUC established by pyroglutamic acid and pyruvic acid in vitreous was 0.951. CONCLUSIONS: These findings have expanded our understanding of identified metabolites and revealed for the first time some novel metabolites in DR. These results may provide useful information to explore the mechanism and may eventually allow the development of metabolic biomarkers for prognosis and novel therapeutic strategies for the management of DR.
AIM: To identify the potential metabolite markers in diabetic retinopathy (DR) by using gas chromatography coupled with time-of-flight mass spectrometry (GC-TOFMS). METHODS: GC-TOFMS spectra were acquired from vitreous and aqueous humor (AH) samples of patients with DR and non-diabeticparticipants. Comparative analysis was used to elucidate the distinct metabolites of DR. Metabolic pathway was employed to explicate the metabolic reprogramming pathways involved in DR. Logistic regression and receiver-operating characteristic analyses were carried out to select and validate the biomarker metabolites and establish a therapeutic model. RESULTS: Comparative analysis showed a clear separation between disease and control groups. Eight differentiating metabolites from AH and 15 differentiating metabolites from vitreous were highlighted. Out of these 23 metabolites, 11 novel metabolites have not been detected previously. Pathway analysis identified nine pathways (three in AH and six in vitreous) as the major disturbed pathways associated with DR. The abnormal of gluconeogenesis, ascorbate-aldarate metabolism, valine-leucine-isoleucine biosynthesis, and arginine-proline metabolism might weigh the most in the development of DR. The AUC of the logistic regression model established by D-2,3-Dihydroxypropanoic acid, isocitric acid, fructose 6-phosphate, and L-Lactic acid in AH was 0.965. The AUC established by pyroglutamic acid and pyruvic acid in vitreous was 0.951. CONCLUSIONS: These findings have expanded our understanding of identified metabolites and revealed for the first time some novel metabolites in DR. These results may provide useful information to explore the mechanism and may eventually allow the development of metabolic biomarkers for prognosis and novel therapeutic strategies for the management of DR.
Entities:
Keywords:
Aqueous humor; Diabetic retinopathy; Mass spectrometry; Metabolism; Vitreous
Authors: Leen Oyoun Alsoud; Nelson C Soares; Hamza M Al-Hroub; Muath Mousa; Violet Kasabri; Nailya Bulatova; Maysa Suyagh; Karem H Alzoubi; Waseem El-Huneidi; Bashaer Abu-Irmaileh; Yasser Bustanji; Mohammad H Semreen Journal: Metabolites Date: 2022-06-01