Publications by authors named "Jin Sook Yoon"

159 Publications

Longitudinal association of thyroid-stimulating immunoglobulin levels with clinical characteristics in thyroid eye disease.

BMJ Open 2022 06 21;12(6):e050337. Epub 2022 Jun 21.

Department of Ophthalmology, Inje University College of Medicine, Inje University Busan Paik Hospital, Busan, Korea (the Republic of)

Objectives: The clinical course of thyroid eye disease (TED) is heterogeneous and predicting patients who may develop the severe sequelae of the disease is difficult. In this study, we evaluated the longitudinal association between changes in serum thyroid-stimulating hormone (TSH) receptor antibody (TRAb) levels and course of disease activity and severity over time.

Design: This was a multicentre, prospective, observational study.

Setting: Fifteen tertiary care oculoplastic service centres in Korea.

Participants: Seventy-six patients with newly diagnosed TED were included and followed up for 12 months.

Methods: We evaluated clinical characteristics and serum TRAb levels at baseline, 6 and 12 months of TED diagnosis. Additionally, we analysed longitudinal associations between the serum TRAb levels and clinical activity score (CAS), no signs or symptoms, only signs, soft tissue involvement, proptosis, extraocular muscle involvement, corneal involvement, sight loss (NOSPECS) score and proptosis.

Results: Thyroid-stimulating immunoglobulin (TSI) and TSH-binding inhibitory immunoglobulin (TBII) levels decreased during the 1-year follow-up, whereas disease activity measured using CAS decreased mainly in the first 6 months. Disease severity measured using NOSPECS score and proptosis remained unchanged. Moreover, inter-person differences in TBII levels were associated with CAS, NOSPECS score and proptosis over time, whereas inter-person differences in TSI levels were associated with NOSPECS score. Subgroup analysis of patients with a baseline CAS≥4 demonstrated that within-person changes in TSI levels affected the CAS and NOSPECS score.

Conclusions: Follow-up measurement of serum TSI and TBII levels may help evaluate TED prognosis and enable accurate clinical decision-making.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2021-050337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9214404PMC
June 2022

Therapeutic Potential of Targeting Periostin in the Treatment of Graves' Orbitopathy.

Front Endocrinol (Lausanne) 2022 30;13:900791. Epub 2022 May 30.

Department of Ophthalmology, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, Seoul, South Korea.

Periostin is a matricellular protein that is ubiquitously expressed in normal human tissues and is involved in pathologic mechanism of chronic inflammatory and fibrotic disease. In this study we investigate periostin in the pathogenesis of Graves' orbitopathy (GO) using human orbital adipose tissue obtained from surgery and primary cultured orbital fibroblasts . POSTN (gene encoding periostin) expression in Graves' orbital tissues and healthy control tissues was studied, and the role of periostin in GO pathologic mechanism was examined through small-interfering RNA (siRNA)-mediated silencing. POSTN gene expression was significantly higher in Graves' orbital tissues than healthy control tissues in real-time PCR results, and immunohistochemical staining revealed higher expression of periostin in Graves' orbital tissues than normal tissues. Silencing periostin using siRNA transfection significantly attenuated TGF-β-induced profibrotic protein production and phosphorylated p38 and SMAD protein production. Knockdown of periostin inhibited interleukin-1 β -induced proinflammatory cytokines production as well as phosphorylation of NF-κB and Ak signaling protein. Adipocyte differentiation was also suppressed in periostin-targeting siRNA transfected GO cells. We hypothesize that periostin contributes to the pathogenic process of inflammation, fibrosis and adipogenesis of GO. Our study provides evidence that periostin may be a novel potential therapeutic target for the treatment of GO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2022.900791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9189304PMC
May 2022

Potential Therapeutic Role of Bone Morphogenic Protein 7 (BMP7) in the Pathogenesis of Graves' Orbitopathy.

Invest Ophthalmol Vis Sci 2022 06;63(6)

Department of Ophthalmology, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea.

Purpose: We investigated a role of bone morphogenic protein 7 (BMP7), a member of the TGF-β superfamily on pathogenic mechanism of Graves' orbitopathy (GO). The therapeutic effects of BMP7 on inflammation and fibrosis were evaluated in cultured Graves' orbital fibroblasts.

Methods: Expression of BMP7 was compared in cultured orbital tissue explants from GO (n = 12) and normal control (n = 12) subjects using real-time PCR. Orbital fibroblasts were cultured from orbital connective tissues obtained from GO (n = 3) and normal control patients (n = 3). Cells were pretreated with recombinant human BMP7 (rhBMP7) before stimulation with TGF-β, IL-1β, and TNF-α. Fibrosis-related proteins and inflammatory cytokines were analyzed by Western blotting. The activation of signaling molecules in inflammation and fibrosis was also analyzed.

Results: The expressions of BMP7 mRNA were lower in GO orbital tissues than control. Fibrosis-related proteins, fibronectin, collagen 1α, and α-SMA induced by TGF-β were suppressed by treating rhBMP7, and rhBMP7 upregulated TGF-β induced SMAD1/5/8 protein expression, whereas downregulated SMAD2/3. Increased pro-inflammatory molecules, IL-6, IL-8, and intercellular adhesion molecule-1 (ICAM-1) by IL-1β or TNF-α were blocked by rhBMP7 treatment, and the expression of phosphorylated NFκB and Akt was suppressed by rhBMP7 treatment.

Conclusions: BMP7 transcript levels were downregulated in Graves' orbital tissues. Exogenous BMP7 treatment showed inhibitory effects on the production of profibrotic proteins and proinflammatory cytokines in orbital fibroblasts. Our results provide a molecular basis of BMP7 as a new potential therapeutic agent through the opposing mechanism of profibrotic TGF-β/SMAD signaling and proinflammatory cytokine production.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/iovs.63.6.7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9187939PMC
June 2022

Thyroid eye disease: From pathogenesis to targeted therapies.

Taiwan J Ophthalmol 2022 Jan-Mar;12(1):3-11. Epub 2022 Jan 21.

Division of Oculofacial Plastic and Reconstructive Surgery, University of California San Diego, California, United States of America.

Thyroid eye disease (TED) is the most common extrathyroidal manifestation of autoimmune Graves' hyperthyroidism. TED is a debilitating and potentially blinding disease with unclear pathogenesis. Autoreactive inflammatory reactions targeting orbital fibroblasts (OFs) lead to the expansion of orbital adipose tissues and extraocular muscle swelling within the fixed bony orbit. There are many recent advances in the understating of molecular pathogenesis of TED. The production of autoantibodies to cross-linked thyroid-stimulating hormone receptor and insulin-like growth factor-1 receptor (IGF-1R) activates OFs to produce significant cytokines and chemokines and hyaluronan production and to induce adipocyte differentiation. In moderately severe active TED patients, multicenter clinical trials showed that inhibition of IGF-1R with teprotumumab was unprecedentedly effective with minimal side effects. The emergence of novel biologics resulted in a paradigm shift in the treatment of TED. We here review the literature on advances of pathogenesis of TED and promising therapeutic targets and drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/tjo.tjo_51_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8988977PMC
January 2022

Thyroid eye disease reactivation associated with COVID-19 vaccination.

Taiwan J Ophthalmol 2022 Jan-Mar;12(1):93-96. Epub 2022 Feb 28.

Shiley Eye Institute, University of California San Diego, La Jolla, CA, USA.

To describe the presentation of both new-onset and reactivation of thyroid eye disease (TED) following COVID-19 vaccination. Single-institution retrospective case series of patients presenting with symptoms and signs of new or reactivated TED coinciding with recent COVID-19 vaccination. Data collected included patient age, gender, presenting symptoms, ocular history, clinical signs, and interval duration between vaccination and onset of ocular symptoms. Three female patients were identified. All patients were over 18 years of age (range 45-66 years). Patients received either the Moderna or Pfizer COVID-19 vaccine and presented with symptoms of TED within 24 h to 21 days of receiving their first or second dose. None of the patients had previous infections with severe acute respiratory syndrome coronavirus 2. Two patients had a history of inactive TED with stable thyroid function tests: One of these patients had stable disease for at least 15 years and the other had stable disease for 5 years. The third patient had no previous history of thyroid dysfunction or TED and presented with low levels of thyroid-stimulating hormone. All three cases presented with proptosis. In two of three cases, periorbital edema, eyelid retraction, and diplopia were present. None were current smokers. One had prior facial hyaluronic acid filler injections. Symptoms in all cases were improving at 4 to 8 months. While the possibility of unrelated TED flaring concurrently with COVID-19 vaccination exists, questions remain on the effects of the COVID-19 vaccine in patients with autoimmune ophthalmic diseases. Physicians should be aware of this potential association and counsel patients appropriately.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/tjo.tjo_61_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8988971PMC
February 2022

Quantitative assessment of increase in orbital volume after orbital floor fracture reconstruction using a bioabsorbable implant.

Graefes Arch Clin Exp Ophthalmol 2022 Mar 9. Epub 2022 Mar 9.

Department of Ophthalmology, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

Purpose: To assess the postoperative changes in the orbital volume and the degree of enophthalmos after orbital floor fracture reconstruction using a bioabsorbable implant and to determine the predictors of postoperative orbital volume change.

Methods: Single-center, retrospective case series of 16 patients who underwent orbital floor fracture reconstruction using a bioabsorbable implant [poly(L-lactic acid)-poly(glycolic acid)/β-tricalcium phosphate; Biobsorb β] were included. Three-dimensional volumetric calculations of orbit were determined using computed tomography scans and the degree of enophthalmos was assessed via Hertel exophthalmometry. Postoperative changes in the orbital volume and the degree of enophthalmos and their correlation were assessed.

Results: The mean volume of fractured orbits immediately after surgery was 22.26 ± 1.98 cm, increasing to 23.67 ± 2.00 cm at 6-month follow-up (p < 0.001); the increased orbital volume was associated with postoperative deformation of the implant. The mean degree of enophthalmos was 0.09 ± 0.27 mm at 1-month follow-up, which increased to 0.66 ± 0.30 mm at 6-month follow-up (p = 0.001). Increase in orbital volume and enophthalmos progression showed a linear correlation (R = 0.682, p = 0.004). Patients with more herniated orbital tissue preoperatively showed increased postoperative orbital volume change (p = 0.015), whereas the size of the fracture area was not predictive of postoperative orbital volume change (p = 0.442).

Conclusion: Increase in orbital volume by deformation of the bioabsorbable implant resulted in progressive enophthalmos during the postoperative follow-up period after orbital floor fracture reconstruction. Thus, careful selection of proper implants before surgery and close postoperative follow-up is needed for an optimal outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00417-022-05610-zDOI Listing
March 2022

Social determinants associated with loss of an eye in the United States using the nationwide database.

Orbit 2021 Dec 30:1-6. Epub 2021 Dec 30.

Division of Ophthalmology Informatics and Data Science, Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California San Diego, La Jolla, California, USA.

Purpose: To identify common factors associated with the loss of an eye using the NIH All of Us database.

Methods: In this case-controlled study, we extracted electronic health record and socio-demographic data for 231 cases of eye loss from All of Us enrollment sites. Controls (N = 924) matched the demographic characteristics of the 2020 United States Census. Bivariate analyses and multivariable logistic regression identified variables significantly associated with increased odds of eye loss.

Outcome Measures: Medical and social determinants associated with increased odds of losing an eye.

Results: Among cases, the average age (standard deviation) was 60.1 (14.4) years. The majority (125, 54.1%) were male. 87 (37.7%) identified as African American, and 49 (21.2%) identified as Hispanic or Latino. Loss of eye was more likely in those with ocular tumor (odds ratio [OR] 421.73, 25 95% confidence interval [CI] 129.81-1959.80, p < .001), trauma (OR 13.38, 95% CI 6.64-27.43, p < .001), infection (OR 11.46, 95% CI 4.11-32.26, p = .001) or glaucoma (OR 8.33, 95% CI 4.43- 15.81, p < .001). African American (OR 2.39, 95% CI 1.39-4.09, p = .002) and Hispanic or Latino (OR 1.80, 95% CI 1.01-3.15, p = .04) participants were disproportionately affected.

Conclusions: Racial and ethnic disparities exist among those with loss of an eye from underlying conditions. Addressing health inequities may mitigate the risk of this morbid outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/01676830.2021.2012205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243193PMC
December 2021

The Effect of CHIR 99021, a Glycogen Synthase Kinase-3β Inhibitor, on Transforming Growth Factor β-Induced Tenon Fibrosis.

Invest Ophthalmol Vis Sci 2021 12;62(15):25

Department of Ophthalmology, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea.

Purpose: This study investigated the effect of glycogen synthase kinase-3β (GSK-3β) inhibition on the fibrosis of human Tenon's fibroblasts (HTFs) induced by transforming growth factor-β (TGF-β).

Methods: Quantitative real-time PCR and Western blot analyses were performed to determine the expression levels of molecules associated with the fibrosis of HTFs by TGF-β (fibronectin, collagen Iα, and α-smooth muscle actin) and GSK-3β. The levels of phosphorylated Smad2 and Smad3 were also analyzed in the presence of the GSK-3β inhibitor CHIR 99021. The wound healing assay was performed to determine the effect of CHIR 99021 on the migration of HTFs. All experiments were conducted using primary cultured HTFs or human tenon tissues obtained from normal subjects and patients with glaucoma.

Results: Treatment with TGF-β resulted in an increase in the levels of molecules associated with the fibrosis of HTFs. The expression levels of these molecules were higher in the tenon tissues obtained from patients with glaucoma than those from normal subjects. When the HTFs were treated with TGF-β, a significant increase in the active form of GSK-3β (Y216) was observed. A significant decrease in the active form of GSK-3β and molecules associated with fibrosis by TGF-β was noted in HTFs treated with CHIR 99021. CHIR 99021 treatment reduced the phosphorylated Smad2/Smad2 and phosphorylated Smad3/Smad3 ratios in HTFs and attenuated HTF migration.

Conclusions: Our results demonstrated the effect of GSK-3β inhibition on the regulation of TGF-β-mediated fibrosis of HTFs, suggesting GSK-3β to be a potential target for maintaining bleb function after glaucoma filtration surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/iovs.62.15.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8711002PMC
December 2021

Serum Selenium Levels in Patients with Graves Disease: Associations with Clinical Activity and Severity in a Retrospective Case-control Study.

Korean J Ophthalmol 2022 02 8;36(1):36-43. Epub 2021 Nov 8.

Department of Ophthalmology, Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea.

Purpose: To compare serum selenium levels in Graves patients and non-Graves control participants and to evaluate associations between serum selenium levels and clinical features of Graves orbitopathy (GO).

Methods: We conducted a single-center, retrospective case-control study among 33 patients with Graves disease without GO (GD), 31 patients with diagnosed GO, and 27 unaffected healthy participants enrolled between 2013 and 2020 at Severance Hospital. We compared serum selenium concentrations between the GD, GO, and healthy control groups, and analyzed associations between serum selenium and GO patients' clinical activity scores, severity (assessed through modified NOSPECS scores), and other clinical features using multivariate linear regression analysis.

Results: Mean serum selenium levels were 109.30 ± 16.39, 111.39 ± 14.04, and 126.09 ± 21.09 ng/mL in GO patients, GD patients, and healthy control participants, respectively. Mean serum selenium levels in Graves patients with and without orbitopathy were significantly lower than those in the healthy control group (p < 0.05), and mean selenium levels were slightly lower in GO than those in GD patients (p = 0.594). Serum selenium levels were significantly lower in GO patients with eyelid retraction than in patients without retraction (p = 0.038). However, serum selenium levels were not associated with clinical activity scores and modified NOSPECS scores (p = 0.241 and 0.801, respectively).

Conclusions: Serum selenium levels were significantly lower in Graves patients with or without GO, compared to non-Graves control participants. Selenium levels were not associated with clinical activity scores or NOSPECS scores, though we observed an association with eyelid retraction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3341/kjo.2021.0146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8849989PMC
February 2022

Association of fibroblast growth factor 10 with the fibrotic and inflammatory pathogenesis of Graves' orbitopathy.

PLoS One 2021 12;16(8):e0255344. Epub 2021 Aug 12.

Department of Ophthalmology, Severance Hospital, The Institute of Vision Research, Yonsei University College of Medicine, Seoul, Republic of Korea.

Purpose: The role of fibroblast growth factor (FGF) in orbital fibroblasts (OFs) is rarely known. In this study, we investigated the effect of FGF10 on fibrosis and the inflammation mechanism of Graves' orbitopathy (GO).

Methods: Orbital tissue from GO (n = 15) and non-GO (n = 15) was obtained for this study. The mRNA and protein expression levels of FGF10 and FGF receptor 2b (FGFR2b) in orbital tissue were determined by real-time polymerase chain reaction, western blot analysis, and confocal microscopy. The effects of FGF10 on transforming growth factor (TGF)-β1 induced fibrotic proteins and interleukin (IL)-1β- or tumor necrosis factor (TNF)-α- induced inflammatory proteins were investigated using recombinant human (rh) FGF10 and small interfering (si) RNA transfection against FGF10.

Results: FGF10 and FGFR2b mRNA expression levels were significantly lower in GO orbital tissues than in non-GO orbital tissues (p = 0.009 and 0.005, respectively). Immunostaining of FGF10 in orbital adipose tissues showed differences in FGF10 expression between GO and control samples. Immunostaining of FGF10 was very weak in the orbital tissues of GO patients. TGF-β1-induced fibronectin, collagen Iα, α-smooth muscle actin protein expression in GO OFs was attenuated by rhFGF10 treatment and increased by knockdown of FGF10 via siFGF10 transfection. Similarly, IL-1β- or TNF-α-induced IL-6, IL-8, and cyclooxygenase-2 protein production in GO OFs was either blocked by rhFGF10 treatment or further upregulated by inhibition of FGF10 via siFGF10 transfection.

Conclusions: Our data demonstrate that FGF10 has beneficial effects on the inflammatory and fibrotic mechanisms of GO in primary cultured OFs, providing new insights into GO pathology and the discovery of FGF10 as a promising novel therapeutic application for the treatment of GO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255344PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360584PMC
November 2021

Wnt signalling inhibits adipogenesis in orbital fibroblasts from patients with Graves' orbitopathy.

Br J Ophthalmol 2022 07 30;106(7):1019-1027. Epub 2021 Jun 30.

Department of Ophthalmology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Republic of Korea

Background/aims: To investigate the role of Wnt signalling in adipogenesis using an in vitro model of Graves' orbitopathy (GO).

Methods: Orbital fat was obtained from patients with GO and non-GO participants for primary orbital fibroblast (OF) culture. Expression levels of Wnt5a, Wnt10b, β-catenin, phospho-β-catenin and cyclin D1 were compared between GO and non-GO OFs. These expression levels were also determined during adipogenesis of GO and non-GO OFs. The effects of a stimulator and inhibitor of Wnt signalling on adipogenesis of GO and non-GO OFs were investigated.

Results: Western blotting analysis showed significant reductions in β-catenin and cyclin D1 and significant enhancement of phospho-β-catenin in OFs from patients with GO, compared with OFs from non-GO participants (p<0.05). Expression of Wnt5a, Wnt10b, β-catenin and cyclin D1 in OFs was highest on day 0, and then gradually declined after induction of adipogenic differentiation. The expression levels of PPARγ, C/EBPα and C/EBPβ were reduced in Wnt stimulator-treated OFs in a dose-dependent manner. Oil red O staining confirmed that a stimulator of Wnt inhibited adipogenesis in GO OFs.

Conclusion: These results indicate that Wnt signalling inhibits adipogenesis in OFs from patients with GO and non-GO participants. Further studies are required to examine the potential of Wnt signalling as a target for therapeutic strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bjophthalmol-2020-316898DOI Listing
July 2022

Signal transducer and activator of transcription 3 as a potential therapeutic target for Graves' orbitopathy.

Mol Cell Endocrinol 2021 08 9;534:111363. Epub 2021 Jun 9.

Department of Ophthalmology, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, Seoul, 03722, South Korea. Electronic address:

The roles of signal transducer and activator of transcription 3 (STAT3) in inflammation, oxidative stress, and adipogenesis during Graves' orbitopathy (GO) are incompletely understood. Here, STAT3 expression in orbital tissues (from individuals with GO and healthy control subjects) was studied, and the role of STAT3 in GO pathogenesis was examined through small-interfering RNA (siRNA)-mediated silencing in primary orbital fibroblasts. STAT3 mRNA expression was higher in GO orbital tissues than in non-GO tissues. Treatment with proinflammatory cytokines, thyroid-stimulating hormone, or insulin-like growth factor-1 induced STAT3 mRNA in GO orbital fibroblasts, but not in non-GO cells. STAT3 silencing inhibited interleukin-1β-induced inflammatory cytokines and oxidative stress-induced haem oxygenase-1 expression. STAT3 siRNA-transfected GO orbital fibroblasts showed decreased adipocyte differentiation. STAT3 affected proinflammatory cytokine production, oxidative stress responses, and adipogenesis in an in vitro model of GO, suggesting that STAT3 mediates GO pathology, and that modulating STAT3 expression may have therapeutic potential against GO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mce.2021.111363DOI Listing
August 2021

A Case of Complication After Conjoint Fascial Sheath Suspension.

Ophthalmic Plast Reconstr Surg 2021 May-Jun 01;37(3S):S113-S114

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/IOP.0000000000001745DOI Listing
May 2021

Correction to: Gene expression profiles of pro-inflammatory mediators in the conjunctiva of patients with epiblepharon.

Graefes Arch Clin Exp Ophthalmol 2021 Jul;259(7):2055

Department of Ophthalmology, Severance Hospital, The Institute of Vision Research, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00417-021-05197-xDOI Listing
July 2021

PERK mediates oxidative stress and adipogenesis in Graves' orbitopathy pathogenesis.

J Mol Endocrinol 2021 05 11;66(4):313-323. Epub 2021 May 11.

Department of Ophthalmology, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea.

We examined endoplasmic reticulum (ER) stress-related gene expression in orbital tissues from patients with Graves' orbitopathy (GO) and the effects of silencing protein kinase RNA-like endoplasmic reticulum kinase (PERK) in primary orbital fibroblast cultures to demonstrate the therapeutic potential of PERK-modulating agents in GO management. The expression of ER stress-related genes in orbital tissue harvested from individuals with or without GO was studied using real-time PCR. The role of PERK in GO pathogenesis was examined through small-interfering RNA (siRNA)-mediated silencing in cultured primary orbital fibroblasts. Intracellular reactive oxygen species (ROS) levels induced in response to cigarette smoke extract (CSE) or hydrogen peroxide were measured using 5-(and 6)-carboxy-20,70-dichlorodihydrofluorescein diacetate staining and flow cytometry. Cells were stained with Oil Red O, and adipogenesis-related transcription factor expression was evaluated through Wwestern blotting after adipogenic differentiation. PERK, activating transcription factor 4 (ATF4), and CCAAT-enhancer-binding protein (C/EBP)-homologous protein (CHOP) mRNA levels were significantly higher in GO orbital tissues than in non-GO orbital tissues. PERK silencing inhibited CSE- or hydrogen peroxide-induced ROS generation. After adipogenic differentiation, GO orbital fibroblasts revealed decreased lipid droplets and downregulation of C/EBPα, C/EBPβ, and peroxisome proliferator-activator gamma (PPARγ) in PERK siRNA-transfected cells. The orbital tissues of patients with GO were exposed to chronic ER stress and subsequently exhibited enhanced unfolded protein response (especially through the PERK pathway). PERK silencing reduced oxidative stress and adipogenesis in GO orbital fibroblasts in vitro. Our results imply that PERK-modulating agents can potentially be used to manage GO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/JME-21-0057DOI Listing
May 2021

Gene expression profiles of pro-inflammatory mediators in the conjunctiva of patients with epiblepharon.

Graefes Arch Clin Exp Ophthalmol 2021 Jul 5;259(7):2027-2033. Epub 2021 Feb 5.

Department of Ophthalmology, Yongin Severance Hospital, The Institute of Vision Research, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

Purpose: To investigate the gene expression of pro-inflammatory mediators in the conjunctiva of pediatric patients with epiblepharon in a case-control study.

Methods: Twenty healthy controls and 15 pediatric patients with epiblepharon were enrolled from April 23, 2020 to June 15, 2020. Epiblepharon severity was divided into class I-III (least to moderate severity) and class IV (most severe). We obtained impression cytologic specimens from the medial palpebral conjunctiva of the participants to measure the gene expression of interleukin (IL)-1β, IL-6, matrix metalloproteinase 9 (MMP9), and mucin 5AC (MUC5AC) using quantitative reverse transcription polymerase chain reaction.

Results: The mean age in the epiblepharon group was 9 years (range 7.5-11 years), and that in the healthy control group was 9.5 years (range 8-11.3 years). IL-1β, IL-6, and MMP9 expression levels were 2.08 (p < 0.05), 2.11 (p < 0.05), and 2.48 (p < 0.05) fold higher, respectively, in the epiblepharon group than in the healthy control group. However, MUC5AC gene expression was not different between healthy subjects and patients with epiblepharon. IL-1β, IL-6, and MMP9 expression levels in class IV patients were 1.32 (p < 0.05), 1.77 (p < 0.05), and 1.98 (p < 0.05) fold higher, respectively, than in class I-III patients.

Conclusion: Epiblepharon may induce chronic inflammatory changes in the conjunctiva in addition to corneal epithelial damage. Therefore, early corrective surgery should be considered to prevent conjunctival inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00417-021-05089-0DOI Listing
July 2021

Role of Proprotein Convertase Subtilisin/Kexin Type 9 in the Pathogenesis of Graves' Orbitopathy in Orbital Fibroblasts.

Front Endocrinol (Lausanne) 2020 8;11:607144. Epub 2021 Jan 8.

Department of Ophthalmology, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, Seoul, South Korea.

Background: The proprotein convertase subtilisin/kexin type 9 (PCSK9) has been implicated in the pathogenesis of inflammatory diseases. We sought to investigate the role of PCSK9 in the pathogenesis of Graves' orbitopathy (GO) and whether it may be a legitimate target for treatment.

Methods: The was compared between GO (n=11) and normal subjects (n=7) in orbital tissue explants using quantitative real-time PCR, and in cultured interleukin-1β (IL-1β)-treated fibroblasts using western blot. Western blot was used to identify the effects of PCSK9 inhibition on IL-1β-induced pro-inflammatory cytokines production and signaling molecules expression as well as levels of adipogenic markers and oxidative stress-related proteins. Adipogenic differentiation was identified using Oil Red O staining. The plasma PCSK9 concentrations were compared between patients with GO (n=44) and healthy subjects (n=26) by ELISA.

Results: The transcript level was higher in GO tissues. The depletion of PCSK9 blunted IL-1β-induced expression of intercellular adhesion molecule 1 (ICAM-1), IL-6, IL-8, and cyclooxygenase-2 (COX-2) in GO and non-GO fibroblasts. The levels of activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and phosphorylated forms of Akt and p38 were diminished when PCSK9 was suppressed in GO fibroblasts. Decreases in lipid droplets and attenuated levels of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein β (C/EBPβ), and leptin as well as hypoxia-inducible factor 1α (HIF-1α), manganese superoxide dismutase (MnSOD), thioredoxin (Trx), and heme oxygenase-1 (HO-1) were noted when PCSK9 was suppressed during adipocyte differentiation. The plasma PCSK9 level was significantly higher in GO patients and correlated with level of thyrotropin binding inhibitory immunoglobulin (TBII) and the clinical activity score (CAS).

Conclusions: PCSK9 plays a significant role in GO. The PCSK9 inhibition attenuated the pro-inflammatory cytokines production, oxidative stress, and fibroblast differentiation into adipocytes. PCSK9 may serve as a therapeutic target and biomarker for GO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2020.607144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821242PMC
May 2021

Endoscopic transorbital approach to the insular region: cadaveric feasibility study and clinical application (SevEN-005).

J Neurosurg 2021 Jan 22:1-9. Epub 2021 Jan 22.

5Department of Neurosurgery, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea.

Objective: The insula is a complex anatomical structure. Accessing tumors in the insula remains a challenge due to its anatomical complexity and the high chance of morbidity. The goal of this study was to evaluate the feasibility of an endoscopic transorbital approach (ETOA) to the insular region based on a cadaveric study.

Methods: One cadaveric head was used to study the anatomy of the insula and surrounding vessels. Then, anatomical dissection was performed in 4 human cadaveric heads using a dedicated endoscopic system with the aid of neuronavigation guidance. To assess the extent of resection, CT scanning was performed before and after dissection. The insular region was directly exposed by a classic transcranial approach to check the extent of resection from the side with a classic transcranial approach.

Results: The entire procedure consisted of two phases: an extradural orbital phase and an intradural sylvian phase. After eyelid incision, the sphenoid bone and orbital roof were extensively drilled out with exposure of the frontal and temporal dural layers. After making a dural window, the anterior ramus of the sylvian fissure was opened and dissected. The M2 segment of the middle cerebral artery (MCA) was identified and traced posterolaterally. A small corticectomy was performed on the posterior orbital gyrus. Through the window between the lateral lenticulostriate arteries and M2, the cortex and medulla of the insula were resected in an anteroposterior direction without violation of the M2 segment of the MCA or its major branches. When confirmed by pterional craniotomy, the sylvian fissure and the MCA were found to be anatomically preserved. After validation of the feasibility and safety based on a cadaveric study, the ETOA was successfully performed in a patient with a high-grade glioma (WHO grade III) in the right insula.

Conclusions: The transorbital route can be considered a potential option to access tumors located in the insula. Using an ETOA, the MCA and its major branches were identified and preserved while removal was performed along the long axis of the insula. In particular, lesions in the anterior part of the insula are most benefited by this approach. Because this approach was implemented in only one patient, additional discussion and further verification is required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2020.8.JNS202255DOI Listing
January 2021

A Pilot Clinical Study of Ocular Prosthesis Fabricated by Three-dimensional Printing and Sublimation Technique.

Korean J Ophthalmol 2021 02 11;35(1):37-43. Epub 2020 Dec 11.

Department of Ophthalmology, Institute of Vision Research, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Purpose: We sought to evaluate the safety and effectiveness of patient-specific ocular prostheses produced by three-dimensional (3D) printing and the sublimation technique. A comparison with prostheses produced using manual manufacturing methods was then performed.

Methods: To confirm the biological and physiochemical safety, cytotoxicity, systemic acute toxicity, intradermal reaction, and skin sensitization tests were conducted according to the International Organization for Standardization guidelines. The compressive strength of the prostheses was also tested. Further, a case series of three patients who wore the 3D printed prostheses for more than eight hours daily for 4 weeks was executed. Self-assessments by these individuals using a questionnaire and safety evaluations focusing on the occurrence of conjunctival inflammation or allergic reactions according to the Cornea and Contact Lens Research Unit criteria by slit-lamp examination and similarity assessment were completed.

Results: The 3D printed ocular prostheses met the necessary qualifications per the biological and physiochemical safety tests, showing the absence of cytotoxicity, acute systemic toxicity, intradermal reactivity, and skin-sensitizing potency. Also, there was no difference in strength test results between previous ocular prostheses and the 3D printed ones. Self-assessment by the patients yielded satisfactory results, with no significant difference in the level of satisfaction reported for the 3D printed and previous handmade ocular prostheses. The 3D printed prosthesis did not trigger any side effects in the conjunctival sac and showed similar objective findings with respect to the color of the iris, sclera, and vessel patterns.

Conclusions: Our study confirms the biologic and physiochemical safety of 3D-printed ocular prostheses created using computer-aided design technology and a sublimation technique. The patients' questionnaires and the judgment of the ophthalmologists/ocularists showed that the 3D printed ocular prosthesis was acceptable in function and appearance through a case series report.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3341/kjo.2020.0125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904411PMC
February 2021

Role of binding immunoglobulin protein (BiP) in Graves' orbitopathy pathogenesis.

J Mol Endocrinol 2021 01;66(1):71-81

Department of Ophthalmology, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea.

Inflammation and adipogenesis represent the main pathogenic mechanisms of Graves' orbitopathy (GO), and oxidative stress is a well-known inducer of GO pathology. Endoplasmic reticulum (ER) stress has been suggested as a major contributor to inflammation and reactive oxygen species (ROS) generation. In this study, we investigated the role of the ER-stress chaperone protein, binding immunoglobulin protein (BiP), in GO pathogenesis. Using primary cultures of orbital fibroblasts from patients with GO, we examined the role of BiP in GO pathogenesis by silencing its expression with small-interfering RNA (siRNA). Inflammatory cytokine expression was analysed by Western blotting and ELISA. Intracellular ROS levels induced by hydrogen peroxide or cigarette smoke extract were measured by 5-(and 6)-carboxy-20,70-dichlorodihydrofluorescein diacetate staining and flow cytometry. After adipogenic differentiation in BiP siRNA-transfected cells, the cells were stained with Oil Red O, and the levels of adipogenic transcription factors were determined by Western blot analysis. BiP mRNA expression levels were significantly higher in GO orbital tissues than in non-GO orbital tissues. Silencing BiP attenuated the expression of pro-inflammatory cytokines (interleukin-6, intercellular adhesion molecule-1, and monocyte chemotactic protein-1) in primary cultured GO orbital fibroblasts. Silencing BiP also reduced ROS generation, hyaluronan production, and adipocyte differentiation. These findings suggest that ER stress is involved in the aetiology of GO and that modulation of ER stress has therapeutic potential for GO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/JME-20-0155DOI Listing
January 2021

Orbital Venous Malformation Accompanied by Arteriovenous Fistula.

Korean J Ophthalmol 2020 08;34(4):343-345

Department of Ophthalmology, Institute of Vision Research, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3341/kjo.2020.0043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419244PMC
August 2020

A Rare Complication of a Large Emphysema after Orbital Wall Fracture Surgery with Silastic Sheet Implant.

Korean J Ophthalmol 2020 08;34(4):334-335

Department of Ophthalmology, Institute of Vision Research, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3341/kjo.2020.0016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419243PMC
August 2020

Protein tyrosine phosphatase 1B as a therapeutic target for Graves' orbitopathy in an in vitro model.

PLoS One 2020 6;15(8):e0237015. Epub 2020 Aug 6.

Department of Ophthalmology, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea.

Graves' orbitopathy (GO) is characterised in early stages by orbital fibroblast inflammation, which can be aggravated by oxidative stress and often leads to fibrosis. Protein tyrosine protein 1B (PTP1B) is a regulator of inflammation and a therapeutic target in diabetes. We investigated the role of PTP1B in the GO mechanism using orbital fibroblasts from GO and healthy non-GO subjects. After 24 hours of transfection with PTPN1 siRNA, the fibroblasts were exposed to interleukin (IL)-1β, cigarette smoke extract (CSE), H2O2, and transforming growth factor (TGF)-β stimulations. Inflammatory cytokines and fibrosis-related proteins were analysed using western blotting and/or enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) release was detected using an oxidant-sensitive fluorescent probe. IL-1β, tumor necrosis factor (TNF)-α, bovine thyroid stimulating hormone (bTSH), high-affinity human stimulatory monoclonal antibody of TSH receptor (M22), and insulin-like growth factor-1 (IGF-1) significantly increased PTP1B protein production in GO and non-GO fibroblasts. PTPN1 silencing significantly blocked IL-1β-induced inflammatory cytokine production, CSE- and H2O2-induced ROS synthesis, and TGF-β-induced expression of collagen Iα, α-smooth muscle actin (SMA), and fibronectin in GO fibroblasts. Silencing PTPN1 also decreased phosphorylation levels of Akt, p38, and c-Jun N-terminal kinase (JNK) and endoplasmic reticulum (ER)-stress response proteins in GO cells. PTP1B may be a potential therapeutic target of anti-inflammatory, anti-oxidant and anti-fibrotic treatment of GO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237015PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410323PMC
October 2020

Glycogen Synthase Kinase-3β Mediates Proinflammatory Cytokine Secretion and Adipogenesis in Orbital Fibroblasts from Patients with Graves' Orbitopathy.

Invest Ophthalmol Vis Sci 2020 07;61(8):51

,.

Purpose: We sought to determine the role of glycogen synthase kinase-3β (GSK-3β) in the pathogenesis of Graves' orbitopathy(GO).

Methods: Expression of the GSK-3β gene in whole orbital tissue explants was compared between GO and non-GO donors using quantitative real-time PCR (RT-PCR). The expression of proinflammatory molecules in the presence of the GSK-3β inhibitor CHIR 99021 was analyzed using RT-PCR, western blot, and ELISA. Adipogenic differentiation was identified using Oil Red O staining, and the levels of peroxisome proliferator activator gamma (PPARγ) and CCAAT-enhancer-binding proteins (C/EBPs) α and β were determined by western blot.

Results: The expression of GSK-3β was significantly higher in GO tissues than in control tissues. The addition of CHIR 99021 led to a decrease in the active form of the kinase in which the Y216 residue is phosphorylated. When GO and non-GO fibroblasts were stimulated with IL-1β or TNF-α, IL-6, IL-8, intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-1 (COX-1), and monocyte chemoattractant protein 1 (MCP-1) showed increased production, which was blunted when CHIR 99021 was added. The activation of Akt, PI3K, nuclear factor (NF)-κB, Erk, Jnk, and p38 kinase by IL-1β and TNF-α was diminished with CHIR 99021 in GO cells. A decrease in lipid droplets and expression of PPARγ and c/EBPα and -β was noted in fibroblasts treated with CHIR 99021 during adipocyte differentiation. The inhibition of Wnt and β-catenin in adipogenesis was reversed by CHIR 99021.

Conclusions: GSK-3β plays a significant role in GO pathogenesis. The inhibition of the kinase attenuated the proinflammatory cytokines production and fibroblast differentiation into adipocytes. GSK-3β may be a potential target for anti-inflammatory and anti-adipogenic treatment of GO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/iovs.61.8.51DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426624PMC
July 2020

Chemokine Expression during Adipogenesis and Inflammation in Orbital Fibroblasts from Patients with Graves' Orbitopathy.

Korean J Ophthalmol 2020 06;34(3):192-202

Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.

Purpose: Chemokines are involved in the pathogenesis of various autoimmune diseases, including Graves' orbitopathy (GO), but comprehensive analyses of the dynamics of these cytokines and their receptors in such diseases remain lacking. In this study, we investigated the expressions of chemokines and their receptors during adipogenesis and inflammation in primary cultured orbital fibroblasts from patients with GO.

Methods: The messenger RNA (mRNA) expression levels of chemokines were compared between GO (n = 6) and non-GO (n = 5) orbital tissues by real-time polymerase chain reaction. After adipogenesis was induced in primary cultured orbital fibroblasts from patients with GO (n =5) and following stimulation with interleukin (IL)-1β and tumor necrosis factor (TNF)-α, the mRNA expression levels of chemokines and their receptors were analyzed.

Results: Chemokines were significantly downregulated in GO orbital tissues compared to non-GO orbital tissues ( < 0.05). Adipogenesis resulted in a strong increase in mRNA expression levels of chemokines and their receptors at an early stage (day 1); however, expression levels started to decrease thereafter and, eventually, decreased to below basal levels at the end of adipogenesis (day 10). Following stimulation with IL-1β and TNF-α, the mRNA expression levels of chemokines and their receptors increased, showing different responses to various proinflammatory cytokines.

Conclusions: Chemokines were strongly upregulated in the early phase of adipogenesis before decreasing continuously until the end of adipogenesis. Also, overt mature GO tissues showed reduced mRNA expression of chemokines compared to controls, which might indicate the existence of a shorter window for effective medical inflammatory treatment. The heightened levels of chemokines and their receptors observed after stimulation with IL-1β and TNF-α suggest a crucial role of proinflammatory cytokines in the pathogenesis of GO and, further, support the idea that chemokines could be used as biomarkers of GO activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3341/kjo.2020.0002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269740PMC
June 2020

Leptomeningeal Seeding in Choroidal Melanoma after Enucleation Surgery.

Korean J Ophthalmol 2020 04;34(2):176-177

Department of Ophthalmology, Institute of Vision Research, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3341/kjo.2019.0101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105793PMC
April 2020

Therapeutic Effect of Guggulsterone in Primary Cultured Orbital Fibroblasts Obtained From Patients with Graves' Orbitopathy.

Invest Ophthalmol Vis Sci 2020 03;61(3):39

,.

Purpose: Inflammation, hyaluronan production, and adipogenesis are the main pathological events leading to Graves' orbitopathy (GO). Guggulsterone (GS), a phytosterol found in the resin of the guggul plant, is a well-known treatment for several inflammatory disorders, such as arthritis, obesity, and hyperlipidemia. Here we investigated the effects of GS treatment on GO pathology.

Methods: Using primary cultures of orbital fibroblasts from GO patients and non-GO controls, we examined the effects of GS on hyaluronan production and the production of proinflammatory cytokines induced by interleukin (IL)-1β, using real-time reverse transcription-polymerase chain reaction analysis, western blots, and enzyme-linked immunosorbent assays. Further, adipogenic differentiation was evaluated by quantification of Oil Red O staining and assessment of protein levels of peroxisome proliferator activator gamma (PPARγ), CCAAT-enhancer-binding proteins (C/EBP) α and β, and sterol regulatory element-binding protein-1 (SREBP-1).

Results: Treatment with noncytotoxic concentrations of GS resulted in the dose-dependent inhibition of IL-1β-induced inflammatory cytokines, including IL-6, IL-8, MCP-1, and COX-2, at both mRNA and protein levels. The hyaluronan level was also significantly suppressed by GS. Moreover, GS significantly decreased the formation of lipid droplets and expression of PPARγ, C/EBP α/β, and SREBP-1 in a dose-dependent manner. GS pretreatment attenuated the phosphorylation of nuclear factor-kappa B induced by IL-1β.

Conclusions: Our data show significant inhibitory effects of GS on inflammation, production of hyaluronan, and adipogenesis in orbital fibroblasts. To our knowledge, this is the first in vitro preclinical evidence of the therapeutic effect of GS in GO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/iovs.61.3.39DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401490PMC
March 2020

Anti-oxidative and anti-adipogenic effects of caffeine in an in vitro model of Graves' orbitopathy.

Endocr J 2020 Apr 16;67(4):439-447. Epub 2020 Jan 16.

Department of Ophthalmology, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea.

Oxidative stress and adipogenesis play key roles in the pathogenesis of Graves' orbitopathy (GO). In this study, the therapeutic effects of caffeine on the reduction of oxidative stress and adipogenesis were evaluated in primary cultured GO orbital fibroblasts in vitro. Orbital fibroblasts were cultured from orbital connective tissues obtained from individuals with GO. Intracellular reactive oxygen species (ROS) levels induced by hydrogen peroxide or cigarette smoke extract and the expression of anti-oxidative enzymes were measured after caffeine treatment. After adipogenic differentiation and caffeine treatment, cells were stained with Oil Red O and the levels of peroxisome proliferator activator γ (PPARγ), C/EBPα, and C/EBPβ were determined by western blot analysis. Hydrogen peroxide and cigarette smoke extract increased the levels of intracellular ROS and anti-oxidative enzymes, which decreased in a dose-dependent manner upon pretreatment with caffeine in GO orbital fibroblasts. Oil Red-O staining results revealed a decrease in lipid droplets; furthermore, PPARγ, C/EBPα, and C/EBPβ protein expression levels were inhibited upon treatment with caffeine during adipocyte differentiation. In conclusion, caffeine decreased oxidative stress and adipogenesis in GO orbital fibroblasts in vitro. These findings may contribute to the development of new types of caffeine-containing pharmacological agents for use in the management of GO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1507/endocrj.EJ19-0521DOI Listing
April 2020

4-Methylumbelliferone suppresses hyaluronan and adipogenesis in primary cultured orbital fibroblasts from Graves' orbitopathy.

Graefes Arch Clin Exp Ophthalmol 2020 May 3;258(5):1095-1102. Epub 2020 Jan 3.

Department of Ophthalmology, Severance Hospital, The Institute of Vision Research, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-ku, Seoul, 120-752, South Korea.

Purpose: In Graves' orbitopathy (GO), hyaluronan secreted by orbital fibroblasts contributes to orbital tissue expansion. The goal of this research was to evaluate the potential benefit of 4-methylumbelliferone (4-MU), a hyaluronan synthase (HAS) inhibitor, in primary cultured orbital fibroblasts from Graves' orbitopathy.

Methods: We assessed the viability of orbital fibroblasts using a live/dead cell assay. Hyaluronan synthesis was evaluated by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (qPCR). Adipogenesis was assessed by Oil Red O staining and qPCR of adipogenic transcription factors.

Results: In orbital fibroblasts treated with 4-MU (up to 1000 μM), cell viability was preserved by 90%. 4-MU significantly inhibited HAS gene expression and hyaluronan production (*P < 0.05). With respect to adipogenesis, 4-MU suppressed the accumulation of lipids and reduced the number of adipocytes, while decreasing expression of adipogenic transcription factors.

Conclusions: 4-MU represents a promising new therapeutic agent for GO based on its ability to inhibit hyaluronan production and adipogenesis, without decreasing cell viability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00417-019-04528-3DOI Listing
May 2020

Proptosis as a Primary Symptom of Brain Arteriovenous Malformation.

Ophthalmic Plast Reconstr Surg 2020 Mar/Apr;36(2):e53-e54

Department of Neurosurgery and Radiology, Severance Stroke Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Proptosis is a common yet cardinal symptom that may indicate the development of a wide range of diseases. Causes of proptosis are usually classified into vascular, inflammatory, endocrine, and neoplastic. Herein, the authors describe a case where proptosis manifested as the primary and only symptom of a massive brain arteriovenous malformation. Deprived of any other conventional symptoms and signs of a brain arteriovenous malformation, such as headaches, nausea, vision loss, increased ocular pressure, and so on, brain imaging played a key role in confirming the diagnosis of this patient. This case proclaims how imperative it is for ophthalmologists to consider the potential of brain arteriovenous malformation as a cause of proptosis and actively engage in brain imaging for diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/IOP.0000000000001570DOI Listing
March 2021
-->