Classical activation of M1 macrophages with lipopolysaccharide (LPS) is associated with a metabolic switch from oxidative phosphorylation to glycolysis. However, the generalizability of such metabolic remodeling to other modes of M1 macrophage stimulation, e.g. type II interferons (IFNs) such as IFNγ, has remained unknown as has the functional significance of aerobic glycolysis during macrophage activation. Here we demonstrate that IFNγ induces a rapid activation of aerobic glycolysis followed by a reduction in oxidative phosphorylation in M1 macrophages. Elevated glycolytic flux sustains cell viability and inflammatory activity, while limiting reliance on mitochondrial oxidative metabolism. Adenosine triphosphate (ATP) distributed by aerobic glycolysis is critical for sustaining IFN-γ triggered JAK (Janus tyrosine kinase)-STAT-1 (Signal Transducer and Activator of Transcription 1) signaling with phosphorylation of the transcription factor STAT-1 as its signature trait. Inhibition of aerobic glycolysis not only blocks the M1 phenotype and pro-inflammatory cytokine/chemokine production in murine macrophages and also human monocytes/macrophages. These findings extend on the potential functional role of immuno-metabolism from LPS- to IFNγ-linked diseases such as atherosclerosis and autoimmune disease.

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In this study, we demonstrate that TRIM21 influences atherosclerosis via regulation of Th17 responses, with TRIM21 deficiency promoting IL-17 expression and a more fibrous, stable, phenotype of the plaques.

Visual Abstract

Citation: Fang D, Zhang Z, Wei Y, et al. The morphological relationship between dome-shaped macula and myopic retinoschisis: a cross-sectional study of 409 highly myopic eyes. Invest Ophthalmol Vis Sci. 2020;61(3):19. https://doi.org/10.1167/iovs.61.3.19 PURPOSE.The purpose of this study was to analyze the clinical features of dome-shaped macula (DSM) in highly myopic eyes and its morphological relationship with myopic retinoschisis (MRS). METHODS.In this cross-sectional study, 409 eyes of 409 patients with high myopia who had spectral-domain optical coherence tomography (OCT) examinations were included. The associations of DSM with the distribution of MRS and ocular biometry were evaluated. RESULTS.Of 409 eyes, DSM was detected in 64 eyes (15.6%). The eyes with DSM were more myopic (−18.8 ± 3.9 vs. −13.4 ± 5.9; P < 0.001) and had longer axial length (31.7 ± 2.4 vs. 29.5 ± 2.5; P < 0.001) compared with those without DSM. A higher rate of extrafoveal retinoschisis (35.9% vs. 9.6%; P < 0.001) and a lower rate of foveoschisis (10.9% vs. 26.1%; P = 0.01) were detected in the eyes with DSM compared with those without DSM. In the eyes with DSM, MRS was detected in 30 eyes (46.9%). MRS predominantly affected the extrafoveal area (76.7%), especially the base of the dome (82.6%). The extrafoveal retinoschisis was most frequently distributed in the superior quadrant (52.2%). None of the eyes with DSM displayed fovea-only retinoschisis. The ratio of the height and width of the macular bulge was higher in eyes with MRS than those without MRS (0.05 vs. 0.04; P = 0.001). CONCLUSIONS.A DSM is found in highly myopic eyes with a longer axial length. MRS in eyes with DSM is more likely to affect the extrafoveal area, especially the base of the dome. A steeper macular bulge is associated with the occurrence of MRS.

BackgroundTo investigate the anatomic and functional outcomes of pars plana vitrectomy (PPV) with partial tamponade of filtered air for rhegmatogenous retinal detachment (RRD) caused by superior retinal breaks.MethodsRetrospective, comparative, consecutive case series study. Patients with RRD caused by superior retinal breaks undergone PPV with partial tamponade (Group A) and whole tamponade (Group B) of filtered air were included. The main outcomes were primary and final success rates, best corrected visual acuity (BCVA), and rate of postoperative cataract surgery.ResultsForty-one patients (41 eyes) were included in Group A and 36 patients (36 eyes) were included in Group B. There were no significant differences in primary or final success rates between Groups A and B (P = 0.618 and P = 1.000, respectively). The patients in Group A experienced quicker postoperative vision improvement (from the Week 1 follow-up) than the patients in Group B (from the Month 3 follow-up). The postoperative cataract surgery rate of Group A (7/31) was lower than that of Group B (13/26) (P = 0.031).ConclusionsPPV with partial tamponade of air is effective in achieving a high anatomic success rate, quicker postoperative vision improvement, and lower rate of postoperative cataract surgery in RRD caused by superior retinal breaks.

PURPOSE. To investigate alterations in the morphologic, compositional, and biomechanical properties of the internal limiting membrane (ILM) in pathologic myopic foveoschisis (MF) eyes. METHODS. ILM specimens were peeled from 61 eyes with MF and 56 eyes with stage III/IV idiopathic macular hole (IMH) as a control. Samples were analyzed for transmission electron microscopy (TEM), scanning electron microscopy, immunofluorescence, Western blotting, and atomic force microscopy. ILM characteristics were compared between the two groups. RESULTS. TEM findings revealed that thickness of the MF ILMs significantly decreased compared with that of IMH ILMs (0.753 6 0.215 vs. 1.894 6 0.247 lm; P < 0.0001). The vitreal side stiffness of the MF ILMs was markedly higher than that of the IMH ILMs (3.520 6 0.803 vs. 0.879 6 0.230 MPa, P < 0.0001). Comparing with the IMH group, collagen IV exhibited decreased concentration and different immunofluorescence distribution in ILMs of MF eyes, so also protein a3 (IV), a4 (IV), and a5 (IV). The immunofluorescence staining results showed that astrocytes were observed in none of the IMH eyes and in 12 of 16 MF eyes (75%, P < 0.0001). CONCLUSIONS. These alterations in the MF ILMs appear to be associated with Müller cell and astrocyte reactive gliosis. The present findings contribute to a more in-depth understanding of the pathogenesis of MF.