Plasma metabolomic profiling of proliferative diabetic retinopathy

Abstract

Background Proliferative diabetic retinopathy (PDR), a sight-threatening retinopathy, is the leading cause of irreversible blindness in adults. Despite strict control of systemic risk factors, a fraction of patients with diabetes develop PDR, suggesting the existence of other potential pathogenic factors underlying PDR. This study aimed to investigate the plasma metabotype of patients with PDR and to identify novel metabolite markers for PDR. Biomarkers identified from this study will provide scientific insight and new strategies for the early diagnosis and intervention of diabetic retinopathy. Methods A total of 1024 patients with type 2 diabetes were screened. To match clinical parameters between case and control subjects, patients with PDR (PDR, n = 21) or those with a duration of diabetes of ≥10 years but without diabetic retinopathy (NDR, n = 21) were assigned to the present case-control study. Distinct metabolite profiles of serum were examined using liquid chromatography-mass spectrometry (LC-MS). Results The distinct metabolites between PDR and NDR groups were significantly enriched in 9 KEGG pathways ( P < 0.05, impact > 0.1), namely, alanine, aspartate and glutamate metabolism, caffeine metabolism, beta-alanine metabolism, purine metabolism, cysteine and methionine metabolism, sulfur metabolism, sphingosine metabolism, and arginine and proline metabolism. A total of 63 altered metabolites played important roles in these pathways. Finally, 4 metabolites were selected as candidate biomarkers for PDR, namely, fumaric acid, uridine, acetic acid, and cytidine. The area under the curve for these biomarkers were 0.96, 0.95, 1.0, and 0.95, respectively. Conclusions This study suggested that impairment in the metabolism of pyrimidines, arginine and proline were identified as metabolic dysregulation associated with PDR. And fumaric acid, uridine, acetic acid, and cytidine might be potential biomarkers for PDR. Fumaric acid was firstly reported as a novel metabolite marker with no prior reports of association with diabetes or diabetic retinopathy, which might provide insights into potential new pathogenic pathways for diabetic retinopathy. Electronic supplementary material The online version of this article (10.1186/s12986-019-0358-3) contains supplementary material, which is available to authorized users.

Is the Arginase Pathway a Novel Therapeutic Avenue for Diabetic Retinopathy?

“…Comparisons of plasma metabolic profiles from type 2 diabetic patients showed dysregulation of the L-arginine pathway in patients with PDR as compared with those with NPDR [32]. A similar metabolomics profiling study performed with plasma samples from type 2 diabetic patients in China found similar impairment in the metabolism of L-arginine and L-proline in patients with PDR as compared with diabetic patients without retinopathy [33].…”

Serum Metabolomic Signatures Associated with Disease Severity in Allergic Rhinitis

“…In our study, we observed that the levels of cytidine were elevated in the MAR and MSAR group, and the concentrations of cytidine were positively correlated with TNSS and VAS. Cytidine, a pyrimidine molecule, is considered as the precursor of the cytidine triphosphate (CTP), which is vital in the synthesis, interconversion and degradation of DNA, RNA and lipids [32][33]. Previous studies have found that abnormality of pyrimidine metabolism could in uence the cell growth, development and differentiation, such as T cell and B cell [34].…”

Arginase Pathway in Acute Retina and Brain Injury: Therapeutic Opportunities and Unexplored Avenues

“…However, metabolomic profiling of vitreous samples from patients with proliferative DR revealed increases in arginase pathway metabolites, including arginine, ornithine, and proline with the later showing the most pronounced increase (Paris et al, 2015). Furthermore, L-arginine pathway is dysregulated in plasma samples from type 2 diabetic patients with PDR (Sumarriva et al, 2019;Zhu et al, 2019). In addition, another study of vitreous samples collected from patients with proliferative DR found increases in spermine and spermidine levels as compared to non-diabetic controls while putrescine was reduced (Nicoletti et al, 2003).…”