Metabolomics of various samples advancing biomarker discovery and pathogenesis elucidation for diabetic retinopathy

Abstract

Diabetic retinopathy (DR) is a universal microvascular complication of diabetes mellitus (DM), which is the main reason for global sight damage/loss in middle-aged and/or older people. Current clinical analyses, like hemoglobin A1c, possess some importance as prognostic indicators for DR severity, but no effective circulating biomarkers are used for DR in the clinic currently, and studies on the latent pathophysiology remain lacking. Recent developments in omics, especially metabolomics, continue to disclose novel potential biomarkers in several fields, including but not limited to DR. Therefore, based on the overview of metabolomics, we reviewed progress in analytical technology of metabolomics, the prominent roles and the current status of biomarkers in DR, and the update of potential biomarkers in various DR-related samples via metabolomics, including tear as well as vitreous humor, aqueous humor, retina, plasma, serum, cerebrospinal fluid, urine, and feces. In this review, we underscored the in-depth analysis and elucidation of the common biomarkers in different biological samples based on integrated results, namely, alanine, lactate, and glutamine. Alanine may participate in and regulate glucose metabolism through stimulating N-methyl-D-aspartate receptors and subsequently suppressing insulin secretion, which is the potential pathogenesis of DR. Abnormal lactate could cause extensive oxidative stress and neuroinflammation, eventually leading to retinal hypoxia and metabolic dysfunction; on the other hand, high-level lactate may damage the structure and function of the retinal endothelial cell barrier via the G protein-coupled receptor 81. Abnormal glutamine indicates a disturbance of glutamate recycling, which may affect the activation of Müller cells and proliferation via the PPP1CA–YAP–GS–Gln–mTORC1 pathway.

Integrated Analysis of Metabolomics and Lipidomics in Plasma of T2DM Patients with Diabetic Retinopathy

“…Several previous studies revealed the metabolite levels in vitreous or aqueous humor samples from patients with DR, which shared some altered metabolites with the current study [45]. For example, proline, glutamine, and citrulline were significantly increased in vitreous samples of PDR [46,47].…”

Untargeted Multiomics Approach Coupling Lipidomics and Metabolomics Profiling Reveals New Insights in Diabetic Retinopathy

“…Excellent biomarkers should be specific and sensitive, be easily quantified in easy to take biological samples, and exhibit good linearity with the development of disease. Considering the complexity of the pathogenesis of DR, multiple biomarkers are seemingly more suitable than a single optimal one [18]. Regarding the metabolomics analysis, nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) have both been developed.…”

“…MS is often used in tandem with liquid chromatography (LC) or gas chromatography (GC), which are techniques applied to separate metabolites, thereby improving the resolution of isobaric compounds. In addition, LC-MS has become widely used in recent years, as MS has better sensitivity than NMR, allowing a wider spectrum of metabolites to be measured [18].…”

“…To date, a substantial amount of research has reported potential novel biomarkers for DR in human plasma in samples from patients with T1D or T2D with different disease durations and DR stages, including citrulline, indoleacetic acid, 1-methylhistidine, chenodeoxycholic acid, eicosapentaenoic acid, glutamine and glutamic acid, 1,5-gluconolactone, 2deoxyribonic acid, gluconic acid, fumaric acid, uridine, acetic acid, and cytidine [13,18,[20][21][22][23][24][25][26][27][28][29]. Several of these, such as 3,4-dihydroxybutyric acid (3,4-DHBA), were validated as independent risk markers for DR progression in a study of 648 individuals with T1D [27].…”

Electrospun nanofibers synthesis enhancing the activity of energy storage devices/electrochemical and biosensor applications

“…[195]. In their study, Qi et al (2006) produced Ca-alginate microspheres containing bovine serum albumin (BSA) and subsequently incorporated them into a poly (L-lactic acid) (PLLA) W/O emulsion using electrospinning [196]. The inventors demonstrated a successful integration of BSA, while also achieving a sustained release that extended beyond the duration of the bare microspheres.…”