Purpose: To determine the differences of metabolites and metabolic pathways between patients with proliferative diabetic retinopathy (PDR) and without diabetes (nondiabetic controls) in plasma and vitreous, respectively, and to characterize the relationship between plasma and vitreous metabolic profiles. Methods: Liquid chromatography/tandem mass spectrometry technology was performed to distinct metabolite profiles of plasma and vitreous. A total of 139 plasma samples from 88 patients with PDR and 51 nondiabetic controls, as well as 74 vitreous samples from 51 patients with PDR and 23 nondiabetic controls, were screened. Pathway analysis was performed using MetaboAnalyst 5.0. Pearson correlation analysis was used to investigate the correlation of metabolites in vitreous and plasma. Results: After adjusting for age, fasting blood glucose, and urea, in vitreous metabolomes, a total of 76 features distinguished patients with PDR from controls. Fifteen differential metabolites were found in plasma metabolites. Pantothenate and CoA biosynthesis was the common metabolic pathway altered in both plasma and vitreous. Aromatic amino acid metabolism pathways were dysregulated in vitreous of PDR. For four metabolic features, there were positive correlations between vitreous and plasma. Conclusions: Despite great differences between the metabolic profiles of plasma and vitreous in PDR cases, there are also similarities in the change of metabolites and metabolic pathways. Exploring the relationship of metabolomics between vitreous and plasma may help provide new understanding of the mechanism of PDR.

Diabetic retinopathy (DR) is the leading cause of acquired blindness in middle-aged people. The complex pathology of DR is difficult to dissect, given the convoluted cytoarchitecture of the retina. Here, we performed single-cell RNA sequencing (scRNA-seq) of retina from a model of type 2 diabetes, induced in leptin receptor–deficient (db/db) and control db/m mice, with the aim of elucidating the factors mediating the pathogenesis of DR. We identified 11 cell types and determined cell-type-specific expression of DR-associated loci via genome-wide association study (GWAS)-based enrichment analysis. DR also impacted cell-type-specific genes and altered cell-cell communication. Based on the scRNA-seq results, retinaldehyde-binding protein 1 (RLBP1) was investigated as a promising therapeutic target for DR. Retinal RLBP1 expression was decreased in diabetes, and its overexpression in Müller glia mitigated DR-associated neurovascular degeneration. These data provide a detailed analysis of the retina under diabetic and normal conditions, revealing new insights into pathogenic factors that may be targeted to treat DR and related dysfunctions.

Visual impairment and blindness cause substantial functional and social limitations [1–3], and preventing visual disabilities is a major goal of eye care services. In 2020, approximately 43.3 million people are blind globally, and 553 million have varying degrees of visual impairment [4], and as much as 64% of them are in Asia [5]. The causes […]

Purpose. To investigate the hyperreflective foci (HRF) as an inflammatory biomarker using optical coherence tomography angiography (OCTA) in neovascular age‐related macular degeneration (AMD) patients after antivascular endothelial growth factor (anti‐VEGF) treatment and its association with the retinal microcapillary density. Methods. Twenty‐five eyes from 25 patients with neovascular AMD were included in the study. All eyes were imaged with OCTA at baseline (M0) and after 3 consecutive injections (M3; injection performed each month) of anti‐VEGF. The number of HRF in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and outer retina was counted. The vascular density of the fovea, parafovea, and the whole macula, as well as the area of the foveal avascular zone (FAZ), was measured. Results. The mean interval between baseline and follow‐up with OCTA was 93.08 ± 5.00 (range, 85‐101) days. Compared with the baseline, the number of HRF significantly decreased in DCP (7.52 ± 3.06 vs. 3.76 ± 1.48, P < 0.01) and outer retina (12.04 ± 4.91 vs. 5.88 ± 3.32, P < 0.01) after treatment. There was no significant difference for HRF number in the SCP, the vascular density (containing foveal, parafoveal, and whole macular), and FAZ area before and after treatments. Conclusion. The number of HRF in DCP and outer retina might serve as an inflammatory biomarker in patients with neovascular AMD. The reduced HRF possibly represents the alleviation of inflammation after anti‐VEGF treatment in patients with AMD.