Citation: Lee H, Jang H, Choi YA, Kim HC, Chung H. Association between soluble CD14 in the aqueous humor and hyperreflective foci on optical coherence tomography in patients with diabetic macular edema. Invest Ophthalmol Vis Sci. 2018;59:715-721. https://doi.org/10.1167/ iovs. PURPOSE. To investigate the associations between soluble CD14 (sCD14), a cytokine released by microglia and macrophages, and hyperreflective foci (HF) and various characteristics of spectral-domain optical coherence tomography (SD-OCT) in diabetic macular edema (DME).METHODS. Sixty-nine eyes from 51 patients with DME and 28 eyes from 28 control subjects were studied. sCD14 levels in the aqueous humor (AH) were measured using ELISA before bevacizumab injection (IVB), and the associations between sCD14 and visual acuity, the number of HF, retinal volume, and the DME pattern were assessed.RESULTS. sCD14 levels were higher in DME patients than in the control subjects (29.9 6 41.6 pg/mL versus 8.1 6 3.6 pg/mL, P < 0.001). sCD14 levels in diffuse edema were higher than those in focal edema (50.0 6 65.3 pg/mL versus 19.8 6 14.7 pg/mL, P ¼ 0.039). The number of HF in the inner retina of patients with diffuse edema was significantly higher than that in patients with focal edema (4.4 6 2.3 vs. 2.6 6 2.1, P ¼ 0.001), but no difference was found in the outer retina (5.8 6 3.4 vs. 5.0 6 3.9, P ¼ 0.25). According to multivariate analyses, elevated sCD14 levels were associated with an increased inner nuclear layer volume and the total number of HF in all retinal layers on SD-OCT. Reduction of DME following IVB was correlated with reduction in the number of HF in a subset of eyes followed longitudinally in the study (n ¼ 30).CONCLUSIONS. DME patients with diffuse edema exhibit higher sCD14 levels in the AH and more HF in the inner retina than patients with focal edema, indicating severe inflammation. The strong correlation between sCD14 and HF in the inner retina suggests that the HF observed on SD-OCT may be due to activated microglia in DME.Keywords: CD14, hyperreflective foci, diabetic macular edema, diffuse edema type, focal edema type D iabetic macular edema (DME) is the most common cause of vision loss in diabetic retinopathy (DR).1 The disruption of blood-retinal barriers induces the influx of fluid into the retina, resulting in DME.2 Although the pathogenesis of DR is not fully elucidated, inflammatory reactions, including monocyte/macrophage recruitment and microglia activation, are considered among the causative factors of DME. 3CD14 is a cytokine associated with the innate immune response and is expressed in microglia, monocytes, and macrophages.4 CD14 exists in two forms: membrane-bound or soluble (sCD14) 5 ; both forms are related to the activation of the inflammatory response. 6 In DME, the levels of sCD14 are elevated in the aqueous humor (AH) and vitreous humor and are associated with increased levels of VEGF.7 Microglia are resident immune cells in the retina that are involved in the inflammatory changes underlying DR. In DR, microglia p...

No abstract

BackgroundTo identify novel biomarkers related to the pathogenesis of dry age-related macular degeneration (AMD), we adopted a human retinal pigment epithelial (RPE) cell culture model that mimics some features of dry AMD including the accumulation of intra- and sub-RPE deposits. Then, we investigated the aqueous humor (AH) proteome using a data-independent acquisition method (sequential window acquisition of all theoretical fragment ion mass spectrometry) for dry AMD patients and controls.MethodsAfter uniformly pigmented polarized monolayers of human fetal primary RPE (hfRPE) cells were established, the cells were exposed to 4-hydroxy-2-nonenal (4-HNE), followed by Western blotting, immunofluorescence analysis and ELISA of cells or conditioned media for several proteins of interest. Data-dependent acquisition for identification of the AH proteome and SWATH-based mass spectrometry were performed for 11 dry AMD patients according to their phenotypes (including soft drusen and reticular pseudodrusen [RPD]) and 2 controls (3 groups).ResultsIncreased intra- and sub-RPE deposits were observed in 4-HNE-treated hfRPE cells compared with control cultures based on APOA1, cathepsin D, and clusterin immunoreactivity. Additionally, the differential abundance of proteins in apical and basal chambers with or without 4-HNE treatment confirmed the polarized secretion of proteins from hfRPE cells. A total of 119 proteins were quantified in dry AMD patients and controls by SWATH-MS. Sixty-five proteins exhibited significantly altered abundance among the three groups. A two-dimensional principal component analysis plot was generated to identify typical proteins related to the pathogenesis of dry AMD. Among the identified proteins, eight proteins, including APOA1, CFHR2, and CLUS, were previously considered major components or regulators of drusen. Three proteins (SERPINA4, LUM, and KERA proteins) have not been previously described as components of drusen or as being related to dry AMD. Interestingly, the LUM and KERA proteins, which are related to extracellular matrix organization, were upregulated in both RPD and soft drusen.ConclusionsDifferential protein expression in the AH between patients with drusen and RPD was quantified using SWATH-MS in the present study. Detailed proteomic analyses of dry AMD patients might provide insights into the in vivo biology of drusen and RPD.Electronic supplementary materialThe online version of this article (10.1186/s12886-018-0941-9) contains supplementary material, which is available to authorized users.

Neuromorphic computing based on two-dimensional transition-metal dichalcogenides (2D TMDs) has attracted significant attention recently due to their extraordinary properties generated by the atomic-thick layered structure. This study presents sulfur-defect-assisted MoS2 artificial synaptic devices fabricated by a simple sputtering process, followed by a precise sulfur (S) vacancy-engineering process. While the as-sputtered MoS2 film does not show synaptic behavior, the S vacancy-controlled MoS2 film exhibits excellent synapse with remarkable nonvolatile memory characteristics such as a high switching ratio (∼103), a large memory window, and long retention time (∼104 s) in addition to synaptic functions such as paired-pulse facilitation (PPF) and long-term potentiation (LTP)/depression (LTD). The synaptic device working mechanism of Schottky barrier height modulation by redistributing S vacancies was systemically analyzed by electrical, physical, and microscopy characterizations. The presented MoS2 synaptic device, based on the precise defect engineering of sputtered MoS2, is a facile, low-cost, complementary metal-oxide semiconductor (CMOS)-compatible, and scalable method and provides a procedural guideline for the design of practical 2D TMD-based neuromorphic computing.

Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.