Prostaglandin F2α Regulates Adipogenesis by Modulating Extracellular Signal-Regulated Kinase Signaling in Graves' Ophthalmopathy.

Prostaglandin F2α (PGF2α), the first-line anti-glaucoma medication, can cause the deepening of the upper eyelid sulcus due to orbital lipoatrophy. However, the pathogenesis of Graves' ophthalmopathy (GO) involves the excessive adipogenesis of the orbital tissues. The present study aimed to determine the therapeutic effects and underlying mechanisms of PGF2α on adipocyte differentiation. In this study primary cultures of orbital fibroblasts (OFs) from six patients with GO were established. Immunohistochemistry, immunofluorescence, and Western blotting (WB) were used to evaluated the expression of the F-prostanoid receptor (FPR) in the orbital adipose tissues and the OFs of GO patients. The OFs were induced to differentiate into adipocytes and treated with different incubation times and concentrations of PGF2α. The results of Oil red O staining showed that the number and size of the lipid droplets decreased with increasing concentrations of PGF2α and the reverse transcription-polymerase chain reaction (RT-PCR) and WB of the peroxisome proliferator-activated receptor γ (PPARγ) and fatty-acid-binding protein 4 (FABP4), both adipogenic markers, were significantly downregulated via PGF2α treatment. Additionally, we found the adipogenesis induction of OFs promoted ERK phosphorylation, whereas PGF2α further induced ERK phosphorylation. We used Ebopiprant (FPR antagonist) to interfere with PGF2α binding to the FPR and U0126, an Extracellular Signal-Regulated Kinase (ERK) inhibitor, to inhibit ERK phosphorylation. The results of Oil red O staining and expression of adipogenic markers showed that blocking the receptor binding or decreasing the phosphorylation state of the ERK both alleviate the inhibitory effect of PGF2a on the OFs adipogenesis. Overall, PGF2α mediated the inhibitory effect of the OFs adipogenesis through the hyperactivation of ERK phosphorylation via coupling with the FPR. Our study provides a further theoretical reference for the potential application of PGF2α in patients with GO.

TAP1, a potential immune-related prognosis biomarker with functional significance in uveal melanoma.

BACKGROUND: TAP1 is an immunomodulation-related protein that plays different roles in various malignancies. This study investigated the transcriptional expression profile of TAP1 in uveal melanoma (UVM), revealed its potential biological interaction network, and determined its prognostic value. METHODS: CIBERSORT and ESTIMATE bioinformatic methods were used on data sourced from The Cancer Genome Atlas database (TCGA) to determine the correlation between TAP1 expression, UVM prognosis, biological characteristics, and immune infiltration. Gene set enrichment analysis (GSEA) was used to discover the signaling pathways associated with TAP1, while STRING database and CytoHubba were used to construct protein-protein interaction (PPI) and competing endogenous RNA (ceRNA) networks, respectively. An overall survival (OS) prognostic model was constructed to test the predictive efficacy of TAP1, and its effect on the in vitro proliferation activity and metastatic potential of UVM cell line C918 cells was verified by RNA interference. RESULTS: There was a clear association between TAP1 expression and UVM patient prognosis. Upregulated TAP1 was strongly associated with a shorter survival time, higher likelihood of metastasis, and higher mortality outcomes. According to GSEA analysis, various immunity-related signaling pathways such as primary immunodeficiency were enriched in the presence of elevated TAP1 expression. A PPI network and a ceRNA network were constructed to show the interactions among mRNAs, miRNAs, and lncRNAs. Furthermore, TAP1 expression showed a significant positive correlation with immunoscore, stromal score, CD8+ T cells, and dendritic cells, whereas the correlation with B cells and neutrophils was negative. The Cox regression model and calibration plots confirmed a strong agreement between the estimated OS and actual observed patient values. In vitro silencing of TAP1 expression in C918 cells significantly inhibited cell proliferation and metastasis. CONCLUSIONS: This study is the first to demonstrate that TAP1 expression is positively correlated with clinicopathological factors and poor prognosis in UVM. In vitro experiments also verified that TAP1 is associated with C918 cell proliferation, apoptosis, and metastasis. These results suggest that TAP1 may function as an oncogene, prognostic marker, and importantly, as a novel therapeutic target in patients with UVM.

Intraorbital wooden foreign bodies: case series and literature review.

Intraorbital wooden foreign bodies (IOWFBs) constitute a relatively rare ocular trauma, which occupy a special type of intraorbital foreign bodies (IOFBs). Data regarding IOWFBs must be obtained from case reports or small case series due to their rarity. Here, we reported 5 cases of IOWFBs and reviewed the related literatures, which could provide comprehensive information regarding the clinical manifestations, diagnosis, and surgical treatment of IOWFBs. Combined with the published literature, a total of 51 independent cases were counted after we added 5 cases. Among them, the number of male and female patients was 35 and 16 respectively; the mean age was 27.3±18.2 (range 1-66)y. Obviously, the disorder seemed to occur mainly in young and middle-aged people. Because of the diversity in the clinical manifestations and imaging characteristics of IOWFBs, misdiagnosis and missed diagnosis often occur during the initial visit. Delayed diagnosis may lead to a high risk of orbital infection caused by IOWFBs. Surgery is the treatment of choice for most patients; however, the missed diagnosis and residue of foreign bodies after previous surgery cannot be ignored. Therefore, an accurate diagnosis is governed by the detailed trauma history, careful ocular examination, close observation of clinical manifestations, correct imaging diagnosis [e.g., magnetic resonance imaging (MRI) or computerized tomography (CT)], and timely and completely elimination of IOWFBs.

Comparison of 2-wall versus 3-wall orbital decompression against dysthyroid optic neuropathy in visual function: A retrospective study in a Chinese population.

ABSTRACT: To compare visual function of 2-wall (medial and lateral) versus 3-wall (medial, lateral, and inferior) orbital decompression in patients with dysthyroid optic neuropathy (DON).A total of 52 eyes of 37 patients underwent orbital decompression for DON between 2013 and 2019 were retrospectively reviewed. Two- or 3-wall decompression was performed in 31 eyes of 23 patients and 21 eyes of 14 patients, respectively. We examined best-corrected visual acuity (BCVA), visual field mean deviation (MD) and pattern standard deviation (PSD), pattern-reversed visual evoked potential (PVEP) for P100 latency and amplitude at 60 and 15 arcmin stimulation checkerboard size, as well as proptosis using Hertel exophthalmometry.Whether 2-wall or 3-wall decompression, all parameters of visual function were improved after surgery (all P < .05). The improvement in BCVA, MD, and PSD was not statistically significant between groups (all P > .05). Proptosis reduction was higher after 3-wall decompression (P = .011). Mean increase in P100 amplitude after 3-wall decompression was statistically higher than that of after 2-wall decompression at 60 and 15 arcmin (P = .045 and .020, respectively), while the mean decrease in P100 latency was similar between the groups (P = .821 and .655, respectively). Six patients (66.67%) had persistent postoperative diplopia and 1 patient (20%) had new-onset diplopia in 3-wall decompression group, which were higher than in 2-wall decompression group (46.15% persistent postoperative diplopia and no new-onset diplopia).Both 2-wall and 3-wall decompression can effectively improve visual function of patients with DON. Three-wall decompression provides better improvement in P100 amplitude and proptosis, however new-onset diplopia is more common with this surgical technique.