Publications by authors named "Nobuhisa Mizuki"

183 Publications

Vaccination inhibits the human adenoviral transduction in a mouse keratoconjunctivitis model.

Vaccine 2021 Jun 17;39(26):3498-3508. Epub 2021 May 17.

Department of Molecular Biodefense Research, Graduate School of Medicine, Yokohama City University, Yokohama 236-0004, Japan. Electronic address:

Adenovirus infections are a major cause of epidemic keratoconjunctivitis (EKC), which can lead to corneal subepithelial infiltrates and multifocal corneal opacity. In the current study, we investigated the use of an E1/E3-deleted adenovirus serotype 5 (Ad5) vector as a vaccine administered intramuscularly (IM) or intranasally (IN) against subsequent challenges with a luciferase-expressing Ad5 (Ad5-Luci) vector via eyedrop. We evaluated the adaptive immune response to Ad5 vector vaccination and confirmed a robust polyfunctional CD8 T cell response in splenic cells. Neutralizing Ad5 antibodies were also measured in the sera of vaccinated mice as well as Ad5 antibody in the eye wash solutions. Upon challenge with Ad5-Luci vector 8 weeks post the primary immunization, transduction was significantly reduced by > 70% in the vaccinated mice, which was slightly better in IM- vs. that in IN-vaccinated animals. Resistance to subsequent challenge was observed 10 months post primary IM vaccination, with sustained reduction up to 60% in the Ad5-Luci vector transduction. Passive immunization of naive mice with antisera from IM to vaccinated mice subsequently challenged with the Ad5-Luci vector resulted in approximately 40% loss in transduction efficiency. Furthermore, the mice that received IM immunization with or without CD8 T cell depletion showed > 40% and 70% reductions, respectively, in Ad8 genomic copies after Ad8 topical challenge. We conclude that Ad-vector vaccination successfully induced an adaptive immune response that prevented subsequent Ad transduction in the cornea and conjunctiva-associated tissues in a mouse model of adenovirus keratoconjunctivitis, and that both cellular and humoral immunity play an important role in preventing Ad transduction.
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http://dx.doi.org/10.1016/j.vaccine.2021.05.010DOI Listing
June 2021

Comparison of postoperative recurrence rates between levator aponeurosis advancement and external Müller's muscle tucking for acquired blepharoptosis.

J Plast Reconstr Aesthet Surg 2021 Apr 24. Epub 2021 Apr 24.

Department of Plastic and Reconstructive Surgery, Yokohama City University Hospital, 3-9 Fukuura, Kanazawa-ku, Yokohama-shi, Kanagawa 236-0004, Japan.

Treatment options for acquired blepharoptosis include levator resection, levator aponeurosis advancement (LAA), Müller's muscle-conjunctival resection (MMCR), and frontalis suspension. Previously, we reported a technique called external Müller's muscle tucking (EMMT) using the Müller's muscle as a power source. In this study, we compare LAA with EMMT and evaluate the recurrence and reoperation rates. LAA was performed on 96 eyelids in 51 patients. The average follow-up period was 12.2 months, recurrence occurred in four eyelids (4.2%) of three patients, and reoperation was required in one eyelid of one patient (2.0%). EMMT was performed on 94 eyelids in 51 patients, the mean follow-up period was 10.5 months, recurrence occurred in 14 eyelids (15%) of 10 patients, and reoperation was required in three eyelids of two patients (3.9%). A comparison of LAA and EMMT recurrence showed that EMMT was associated with a significantly higher recurrence rate (P = 0.0021). The causes of EMMT recurrence included thinning and fatty degeneration of Müller's muscles, necrosis of ligated Müller's muscles, and less postoperative scar formation. There was no correlation between EMMT recurrence and the severity of the blepharoptosis.
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http://dx.doi.org/10.1016/j.bjps.2021.03.086DOI Listing
April 2021

Prophylactic and therapeutic vaccine against Pseudomonas aeruginosa keratitis using bacterial membrane vesicles.

Vaccine 2021 05 30;39(23):3152-3160. Epub 2021 Apr 30.

Department of Molecular Biodefense Research, Graduate School of Medicine, Yokohama City University, Yokohama 236-0004, Japan. Electronic address:

Purpose: Pseudomonas aeruginosa (P. aeruginosa) infection is one of the major causes of keratitis. However, effective prophylactic and therapeutic vaccines against P. aeruginosa keratitis have yet to be developed. In this study, we explored the use of P. aeruginosa membrane vesicles (MVs) as a prophylactic vaccine as well as the use of immune sera derived from P. aeruginosa MV-immunized animals as a treatment for P. aeruginosa corneal infections in C57BL/6 mice.

Methods: C57BL/6 mice were intramuscularly immunized with P. aeruginosa MVs; the mouse corneas were then scarified and topically infected with several P. aeruginosa strains, followed by determination of corneal clinical score and corneal bacterial load. Next, immune sera derived from P. aeruginosa MV-immunized ICR mice were administered intraperitoneally to naïve C57BL/6 mice, followed by topical P. aeruginosa challenge. Finally, the immune sera were also used as a topical treatment in the mice with established P. aeruginosa corneal infections.

Results: P. aeruginosa-specific IgG and IgA antibodies induced by intramuscular immunization were detected not only in the sera but also in the eye-wash solution. Both active and passive immunization significantly inhibited P. aeruginosa corneal infection. Finally, topical treatment with immune sera in the mice with established P. aeruginosa corneal infections notably decreased the corneal clinical score and corneal bacterial load.

Conclusions: P. aeruginosa keratitis can be attenuated by vaccination of P. aeruginosa MVs and topical application of P. aeruginosa MV-specific immune sera.
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http://dx.doi.org/10.1016/j.vaccine.2021.04.035DOI Listing
May 2021

Pathogenesis of Non-Infectious Uveitis Elucidated by Recent Genetic Findings.

Front Immunol 2021 12;12:640473. Epub 2021 Apr 12.

Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Uveitis is a generic term for inflammation of the uvea, which includes the iris, ciliary body, and choroid. Prevalence of underlying non-infectious uveitis varies by race and region and is a major cause of legal blindness in developed countries. Although the etiology remains unclear, the involvement of both genetic and environmental factors is considered important for the onset of many forms of non-infectious uveitis. Major histocompatibility complex (MHC) genes, which play a major role in human immune response, have been reported to be strongly associated as genetic risk factors in several forms of non-infectious uveitis. Behçet's disease, acute anterior uveitis (AAU), and chorioretinopathy are strongly correlated with MHC class I-specific alleles. Moreover, sarcoidosis and Vogt-Koyanagi-Harada (VKH) disease are associated with MHC class II-specific alleles. These correlations can help immunogenetically classify the immune pathway involved in each form of non-infectious uveitis. Genetic studies, including recent genome-wide association studies, have identified several susceptibility genes apart from those in the MHC region. These genetic findings help define the common or specific pathogenesis of ocular inflammatory diseases by comparing the susceptibility genes of each form of non-infectious uveitis. Interestingly, genome-wide association of the interleukin (IL)23R region has been identified in many of the major forms of non-infectious uveitis, such as Behçet's disease, ocular sarcoidosis, VKH disease, and AAU. The interleukin-23 (IL-23) receptor, encoded by , is expressed on the cell surface of Th17 cells. IL-23 is involved in the homeostasis of Th17 cells and the production of IL-17, which is an inflammatory cytokine, indicating that a Th17 immune response is a common key in the pathogenesis of non-infectious uveitis. Based on the findings from the immunogenetics of non-infectious uveitis, a personalized treatment approach based on the patient's genetic make-up is expected.
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http://dx.doi.org/10.3389/fimmu.2021.640473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072111PMC
April 2021

Corrigendum: Alpha-Arbutin Promotes Wound Healing by Lowering ROS and Upregulating Insulin/IGF-1 Pathway in Human Dermal Fibroblast.

Front Physiol 2021 12;12:659813. Epub 2021 Mar 12.

Department of Ophthalmology and Visual Sciences, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

[This corrects the article DOI: 10.3389/fphys.2020.586843.].
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http://dx.doi.org/10.3389/fphys.2021.659813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006308PMC
March 2021

Tsga8 is required for spermatid morphogenesis and male fertility in mice.

Development 2021 Apr 26;148(8). Epub 2021 Apr 26.

Department of Histology and Cell Biology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.

During spermatogenesis, intricate gene expression is coordinately regulated by epigenetic modifiers, which are required for differentiation of spermatogonial stem cells (SSCs) contained among undifferentiated spermatogonia. We have previously found that KMT2B conveys H3K4me3 at bivalent and monovalent promoters in undifferentiated spermatogonia. Because these genes are expressed late in spermatogenesis or during embryogenesis, we expect that many of them are potentially programmed by KMT2B for future expression. Here, we show that one of the genes targeted by KMT2B, Tsga8, plays an essential role in spermatid morphogenesis. Loss of Tsga8 in mice leads to male infertility associated with abnormal chromosomal distribution in round spermatids, malformation of elongating spermatid heads and spermiation failure. Tsga8 depletion leads to dysregulation of thousands of genes, including the X-chromosome genes that are reactivated in spermatids, and insufficient nuclear condensation accompanied by reductions of TNP1 and PRM1, key factors for histone-to-protamine transition. Intracytoplasmic sperm injection (ICSI) of spermatids rescued the infertility phenotype, suggesting competency of the spermatid genome for fertilization. Thus, Tsga8 is a KMT2B target that is vitally necessary for spermiogenesis and fertility.
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http://dx.doi.org/10.1242/dev.196212DOI Listing
April 2021

Inhaled Corticosteroid and Secondary Glaucoma: A Meta-analysis of 18 Studies.

Allergy Asthma Immunol Res 2021 May;13(3):435-449

Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Purpose: Guidelines and systematic reviews frequently warn of inhaled corticosteroid (ICS)-induced glaucoma. However, most of the published studies deny it.

Methods: We performed a systematic review of randomized, cohort, nested-case control, cross-sectional studies by using Meta-analyses of Observational Studies in Epidemiology statement. Four major databases, PubMed, EMBASE, Cochrane Search Manager, and the Web of Science Core Collection as well as meta-analysis were used. Studies comparing incidence, prevalence and intraocular pressure (IOP) between patients who were treated with and without ICSs were included. A random-model meta-analysis was performed using the inverse variance method.

Results: Out of 623 studies screened, 18 with 31,665 subjects were finally included. No significant difference between the 2 groups was observed for crude glaucoma incidence (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.86-1.04; = 0.26; ² = 0%; for heterogeneity = 0.57) as a primary endpoint, adjusted glaucoma incidence (OR, 0.90; 95% CI, 0.65-1.24; = 0.64), crude prevalence (OR, 1.82; 95% CI, 0.23-14.19; = 0.57), adjusted prevalence (OR, 1.22; 95% CI, 0.50-2.96; = 0.66), IOP change during ICS treatment (mean difference [MD] +0.01 mmHg; 95% CI, -0.19-0.20; = 0.95), and single measurement IOP (MD +0.37 mmHg; 95% CI, -0.24-0.97; = 0.23). Time-to-event analysis for glaucoma development as one of the secondary endpoints (adjusted hazard ratio, 0.52; 95% CI, 0.28-0.96) suggested a reverse association between ICS and glaucoma.

Conclusions: The ophthalmological side effects of ICSs, such as glaucoma and intraocular hypertension, should not be exaggerated.

Trial Registration: University Hospital Medical Information Network Center Clinical Trial Registry Identifier: UMIN000040351.
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http://dx.doi.org/10.4168/aair.2021.13.3.435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984945PMC
May 2021

Tuberculosis Exposure With Risk of Behçet Disease Among Patients With Uveitis.

JAMA Ophthalmol 2021 Apr;139(4):415-422

The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Importance: Although experimental studies support the hypothesis that exposure of infectious agents may trigger an aberrant immune response and contribute to noninfectious uveitis, the association of a definite pathogen with human noninfectious uveitis conditions appears not to have been well established in a population.

Objective: To evaluate associations of tuberculosis infection with risk of several noninfectious uveitis conditions.

Design, Setting, And Participants: These mendelian randomization and observational analyses were conducted with the genetic data of a Chinese cohort enrolled between April 2008 and January 2018 and a Japanese cohort enrolled between January 2002 and June 2009. We recruited participants for T-SPOT.TB (Oxford Immunotec) assays between July and November 2019. The Chinese cohort included patients with uveitis associated with Behçet disease or other uveitis conditions and control participants. The Japanese cohort and the group given T-SPOT.TB assays included individuals with Behçet disease and control participants. Data analyses for this study were completed from July 2019 to January 2020.

Exposures: Genetic variants associated with tuberculosis as natural proxies for tuberculosis exposure.

Main Outcomes And Measures: The primary outcome was the odds ratio (OR) for Behçet disease, estimated by an inverse variance weighted mean of associations with genetically determined tuberculosis susceptibility. The T-SPOT.TB positivity rate was examined in individuals with Behçet disease and compared with that of control participants.

Results: The Chinese cohort included 999 patients with uveitis associated with Behçet disease, 1585 with other uveitis conditions, and 4417 control participants. The Japanese cohort included 611 individuals with Behçet disease and 737 control participants. The group given T-SPOT.TB assays included 116 individuals with Behçet disease and 121 control participants. Of the Chinese individuals with Behçet disease and control participants, 2257 (41.7%) were female and the mean (SD) age was 35.4 (12.5) years. In the Japanese cohort, 564 (41.8%) were female and the mean (SD) age was 39.1 (12.7) years. Genetically determined tuberculosis susceptibility was associated with an increased risk for Behçet disease. The OR for Behçet disease per 2-fold increase in tuberculosis incidence was 1.26 (95% CI, 1.12-1.43; P = 1.47 × 10-4). Replication using the Japanese cohort yielded similar results (OR, 1.16 [95% CI, 1.08-1.26]). In T-SPOT.TB assays, having a positive result, indicating a history of tuberculosis infection, was found to be an independent risk factor for Behçet disease (OR, 2.26 [95% CI, 1.11-4.60]).

Conclusions And Relevance: These human genetic and biomarker data demonstrated that tuberculosis exposure was a risk factor for Behçet disease. This study provides novel evidence linking an infectious agent to the risk of a noninfectious uveitis condition.
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http://dx.doi.org/10.1001/jamaophthalmol.2020.6985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893545PMC
April 2021

Changes in the proportion of clinical clusters contribute to the phenotypic evolution of Behçet's disease in Japan.

Arthritis Res Ther 2021 02 1;23(1):49. Epub 2021 Feb 1.

Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.

Background: We hypothesized that Behçet's disease (BD) consists of several clinical subtypes with different severity, resulting in heterogeneity of the disease. Here, we conducted a study to identify clinical clusters of BD.

Methods: A total of 657 patients registered in the Yokohama City University (YCU) regional BD registry between 1990 and 2018, as well as 6754 patients who were initially registered in the Japanese Ministry of Health, Labour and Welfare (MHLW) database between 2003 and 2014, were investigated. The YCU registry data regarding the clinical manifestations of BD, human leukocyte antigen (HLA) status, treatments, and hospitalizations were analyzed first, followed by similar analyses of the MHLW for validation. A hierarchical cluster analysis was independently performed in both patient groups.

Results: A hierarchical cluster analysis determined five independent clinical clusters in the YCU cohort. Individual counterparts of the YCU clusters were confirmed in the MHLW registry. Recent phenotypical evolutions of BD in Japan, such as increased gastrointestinal (GI) involvement, reduced complete type according to the Japan Criteria, and reduced HLA-B51 positivity were associated with chronologically changing proportions of the clinical clusters.

Conclusions: In this study, we identified independent clinical clusters among BD patients in Japan and found that the proportion of each cluster varied over time. We propose five independent clusters namely "mucocutaneous", "mucocutaneous with arthritis", "neuro", "GI", and "eye."
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http://dx.doi.org/10.1186/s13075-020-02406-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851921PMC
February 2021

New vaccine production platforms used in developing SARS-CoV-2 vaccine candidates.

Vaccine 2021 01 24;39(2):197-201. Epub 2020 Nov 24.

Department of Molecular Biodefense Research, Graduate School of Medicine, Yokohama City University, Yokohama 236-0004, Japan. Electronic address:

The threat of the current coronavirus disease pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is accelerating the development of potential vaccines. Candidate vaccines have been generated using existing technologies that have been applied for developing vaccines against other infectious diseases. Two new types of platforms, mRNA- and viral vector-based vaccines, have been gaining attention owing to the rapid advancement in their methodologies. In clinical trials, setting appropriate immunological endpoints plays a key role in evaluating the efficacy and safety of candidate vaccines. Updated information about immunological features from individuals who have or have not been exposed to SARS-CoV-2 continues to guide effective vaccine development strategies. This review highlights key strategies for generating candidate SARS-CoV-2 vaccines and considerations for vaccine development and clinical trials.
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http://dx.doi.org/10.1016/j.vaccine.2020.11.054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685034PMC
January 2021

A comprehensive overview on the genetics of Behçet's disease.

Int Rev Immunol 2020 Dec 1:1-64. Epub 2020 Dec 1.

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Behçet's disease (BD) is a systemic and inflammatory disease, characterized mainly by recurrent oral and genital ulcers, eye involvement, and skin lesions. Although the exact etiopathogenesis of BD remains unrevealed, a bulk of studies have implicated the genetic contributing factors as critical players in disease predisposition. In countries along the Silk Road, human leukocyte antigen (HLA)-B51 has been reported as the strongest genetically associated factor for BD. Genome-wide association studies, local genetic polymorphism studies, and meta-analysis of combined data from Turkish, Iranian, and Japanese populations have also identified new genetic associations with BD. Among these, other HLA alleles such as , , , and have been found as independent risk factors for BD, whereas and are independent protective alleles for BD. Moreover, other genes have also reached the genome-wide significance level of association with BD susceptibility, including , , , , , , , , and . Also, several rare nonsynonymous variants in , , , and genes have been reported to be involved in BD pathogenesis. According to genetic determinants in the loci outside the MHC region that are contributed to the host defense, immunity, and inflammation pathways, it is suggested that immune responses to the pathogen as an important environmental factor and mucosal immunity contribute to BD susceptibility.
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http://dx.doi.org/10.1080/08830185.2020.1851372DOI Listing
December 2020

Alpha-Arbutin Promotes Wound Healing by Lowering ROS and Upregulating Insulin/IGF-1 Pathway in Human Dermal Fibroblast.

Front Physiol 2020 4;11:586843. Epub 2020 Nov 4.

Department of Ophthalmology and Visual Sciences, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Alpha-arbutin (4-hydroxyphenyl alpha-glucopyranoside) is a known inhibitor of tyrosinase in keratinocytes; however, its effect on other genes and pathways in other skin cells has not been thoroughly investigated. In this study, we investigate the mechanism of alpha-arbutin activity in human dermal fibroblast cultures for 48 h. Results showed that the oxidative stress pathway was activated as alpha-arbutin reduced reactive oxygen species. In addition, we found a high possibility of wound healing and the upregulation of the insulin-like growth factor 1 receptor (IFG1R) pathway. We also investigated the role of the NRF2 gene in mediating the alpha-arbutin response. comparative genomics analysis conducted using our original tool, SHOE, suggested transcription factors with a role in tumor suppression and toxicity response as candidates for regulating the alpha-arbutin-mediated pathway.
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http://dx.doi.org/10.3389/fphys.2020.586843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672191PMC
November 2020

Suction Break During Femtosecond Laser-Assisted Cataract Surgery and Misplaced Laser Beam Delivery to the Corneal Layers.

Int Med Case Rep J 2020 16;13:643-650. Epub 2020 Nov 16.

Department of Ophthalmology, Yokohama City University School of Medicine, Yokohama, Kanazawa, Japan.

A 68-year-old man with senile cataract underwent femtosecond laser-assisted cataract surgery (FLACS) in his left eye. Only anterior capsulotomy and lens fragmentation were planned with a femtosecond laser. Docking of the patient interface and anterior capsulotomy were completed without any complications. During the lens fragmentation process, the patient could not resist the temptation to squeeze his eyes shut, which caused excessive pressure from the eyelids. As the procedure proceeded, a bubble was formed at the edge of the patient interface and became increasingly larger. In addition, wrinkles in the conjunctiva were observed. As the lens fragmentation was approaching the final stage, the surgeon was reluctant to release the foot pedal to stop the laser emission. Finally, the patient interface lost adhesion to the cornea. Owing to the high repetition rate of the laser, the laser beam slipped into the corneal layers. Under an operating microscope, a grid-pattern laser beam trace was observed in the peripheral part of the cornea. As posterior capsule rupture occurred during the lens removal process, IOL insertion was no longer a suitable option. Therefore, scleral fixation of the implanted intraocular lens was performed without any unexpected events. One year postoperatively, the laser beam trace in the corneal layers could still be identified by slit-lamp examination. Nonetheless, since the laser beam trace was limited to the peripheral part of the cornea, and there was no damage to the central cornea, the visual acuity was 20/20. FLACS has significant benefits, especially in challenging cases of cataract surgery, and has well-established built-in safeguards for complications. However, this case study indicates the possibility of a suction break during laser emission and the preoperative risk factors. It demonstrates that recognizing the signs of suction break is necessary to avoid misplacement of the laser beam on the corneal layers.
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http://dx.doi.org/10.2147/IMCRJ.S280403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678819PMC
November 2020

Refractory optic perineuritis related to granulomatosis with polyangiitis treated with intensive immunosuppressive therapy combined with plasma exchange.

Mod Rheumatol Case Rep 2020 01 8;4(1):84-89. Epub 2019 Aug 8.

Department of Hematology and Clinical Immunology, Yokohama City University School of Medicine, Yokohama, Japan.

Optic perineuritis (OPN), which is an inflammatory disorder affecting the optic nerve sheath, is one of the rare complications in granulomatosis with polyangiitis (GPA). Although several groups have reported that immunosuppressive therapies are generally effective against GPA-associated OPN, so far, there is little information as to other options for refractory cases. Here we demonstrate a case of GPA-associated OPN, which is refractory to potent immunosuppressive therapy including high-dose glucocorticoid, intravenous cyclophosphamide and rituximab therapy, and effective application of therapeutic plasma exchange. We also report here that CSF IL-6 levels may serve as a new biomarker for GPA-associated OPN.
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http://dx.doi.org/10.1080/24725625.2019.1649857DOI Listing
January 2020

Nd:YAG Laser Accidentally Hitting the Corneal Layers During Treatment of Posterior Capsule Opacification After Cataract Surgery and Its Postoperative Process.

Int Med Case Rep J 2020 21;13:449-453. Epub 2020 Sep 21.

Department of Ophthalmology, Yokohama City University School of Medicine, Yokohama, Kanazawa, Japan.

Posterior capsule opacification (PCO) is the most common cause of deterioration of vision and contrast sensitivity and glare after cataract surgery. Neodymium (Nd): yttrium aluminum garnet (YAG) laser capsulotomy is an effective and standard procedure to treat these symptoms. The incidence rate of PCO requiring Nd:YAG laser treatment varies and depends on published studies, ranging from 2.2% to 10.0%. Although Nd:YAG laser treatment is largely safe, it still has complications, such as transient increase of intraocular pressure, anterior uveitis, intraocular lenses pitting, cystoid macula edema, endophthalmitis, and retinal detachment. We encountered a rare complication related to Nd:YAG laser treatment, where the laser accidentally hits the cornea. This occurred because the PCO was mistaken for the corneal layers during the laser procedure. This report presents the 3-year post-treatment process, and the findings herein may help raise the awareness of the possibility of this rare complication and provide measures for its treatment.
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http://dx.doi.org/10.2147/IMCRJ.S271669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518776PMC
September 2020

Efficacy and safety of apremilast for 3 months in Behçet's disease: A prospective observational study.

Mod Rheumatol 2021 Jul 16;31(4):856-861. Epub 2020 Oct 16.

Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Objective: To determine the real-world short-term efficacy and safety of apremilast for Behçet's disease (BD).

Methods: The study included patients who received apremilast for refractory oral ulcers in addition to meeting International Study Group criteria for BD or the revised International Criteria for Behçet's Disease. To assess the efficacy of apremilast, Behçet's disease current activity form (BDCAF) and patients' self-perception of their disease activity were monitored for three months. The disease phenotypes, laboratory data, concomitant medication use, and adverse events were also investigated.

Results: Fourteen BD patients were included in the study. Concomitant drug use were as follows: colchicine 92.9%, prednisolone 21.4%, immunosuppressants 28.6%, and tumor-necrosis inhibitor 14.3%. Oral ulcers and BDCAF scores at 3 months showed significant improvement compared to baseline. Adverse events during the study were diarrhea ( = 3, 21.4%), nausea ( = 3, 21.4%), music hallucination ( = 1, 7.1%), and branch retinal vein occlusion ( = 1, 7.1%). Apremilast was discontinued in 1 patient (7.1%) due to nausea.

Conclusion: Significant improvement in oral ulcer and BDCAF with apremilast was confirmed in real-world BD patients after 3 months. The combination of colchicine and apremilast appears to be well tolerated in BD in the short-term.
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http://dx.doi.org/10.1080/14397595.2020.1830504DOI Listing
July 2021

Clinical Characteristics, Management, and Factors Associated with Poor Visual Prognosis of Acute Retinal Necrosis.

Ocul Immunol Inflamm 2020 Sep 18:1-6. Epub 2020 Sep 18.

Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

: To identify the clinical characteristics of acute retinal necrosis (ARN) and clarify factors associated with poor visual prognosis.: a nationwide multi-center retrospective chart review study was performed in Japan using data from the medical records of 149 consecutive ARN patients. Demographics, ocular signs, virologic testing of intraocular fluids, and treatment were examined. Factors associated with poor visual prognosis were investigated by regression analysis.: At initial presentation, anterior chamber cells or mutton-fat keratic precipitates (97%), unilaterality (93%), and yellow-white retinal lesions (86%) were recognized. In the clinical course, rapid circumferential expansion of retinal lesions (39%), development of retinal break or retinal detachment (55%), and optic atrophy (43%) were recorded. Four variables were identified as associated with poor visual prognosis.: The present study identified clinical characteristics and factors associated with poor visual prognosis of ARN.
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http://dx.doi.org/10.1080/09273948.2020.1789179DOI Listing
September 2020

Usefulness of Combined Measurement of Serum Soluble IL-2R and Angiotensin-Converting Enzyme in the Detection of Uveitis Associated with Japanese Sarcoidosis.

Clin Ophthalmol 2020 12;14:2311-2317. Epub 2020 Aug 12.

Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan.

Purpose: Angiotensin-converting enzyme (ACE) is conventionally used as a biomarker in the diagnosis of uveitis associated with sarcoidosis, but its sensitivity is relatively low. In this study, we investigated whether serum soluble interleukin-2 receptor (sIL-2R) is also useful as a diagnostic marker, in addition to ACE, in the detection of uveitis associated with sarcoidosis.

Patients And Methods: Data were analyzed from 126 patients with uveitis (52 sarcoidosis and 74 non-sarcoid uveitis) and 12 with primary intraocular lymphoma (PIOL) who had their serum sIL-2R and ACE levels measured.

Results: Serum sIL-2R level was elevated in 69.2% of patients with sarcoid uveitis, 5.4% of those with non-sarcoid uveitis, and 16.7% of those with PIOL. The sensitivity and specificity of an elevated sIL-2R level for the detection of sarcoidosis were 69.2% and 93.0%, respectively. In contrast, serum ACE levels were elevated only in patients with sarcoid uveitis, with a sensitivity of 44.2% and specificity of 100%. Furthermore, serum sIL-2R and/or ACE level was elevated in 75.0% of patients with sarcoid uveitis, which is higher than those who had elevated serum ACE level only (44.2%, = 0.0025). The sensitivity and specificity of elevated sIL-2R and/or ACE in detecting sarcoid uveitis were 75.0% and 93.0%, respectively. The PPV was 0.87, and the NPV was 0.86.

Conclusion: Compared with the sensitivity of serum ACE levels alone, combined measurement of both serum sIL-2R and ACE levels improves sensitivity in the detection of uveitis associated with sarcoidosis. Nevertheless, serum ACE alone remains useful thanks to its high specificity in the differentiation of uveitis patients, with sarcoidosis from those without sarcoidosis.
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http://dx.doi.org/10.2147/OPTH.S264595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429236PMC
August 2020

The human papillomavirus E6 protein targets apoptosis-inducing factor (AIF) for degradation.

Sci Rep 2020 08 26;10(1):14195. Epub 2020 Aug 26.

Department of Molecular Biodefense Research, Yokohama City University, Yokohama, 236-0004, Japan.

Oncoprotein E6 of high-risk human papillomavirus (HPV) plays a critical role in inducing cell immortalization and malignancy. E6 downregulates caspase-dependent pathway through the degradation of p53. However, the effect of HPV E6 on other pathways is still under investigation. In the present study, we found that HPV E6 directly binds to all three forms (precursor, mature, and apoptotic) of apoptosis-inducing factor (AIF) and co-localizes with apoptotic AIF. This binding induced MG132-sensitive reduction of AIF expression in the presence of E6 derived from HPV16 (16E6), a cancer-causing type of HPV. Conversely, E6 derived from a non-cancer-causing type of HPV, HPV6 (6E6), did not reduce the levels of AIF despite its interaction with AIF. Flow cytometric analysis revealed that 16E6, but not 6E6, suppressed apoptotic AIF-induced chromatin degradation (an indicator of caspase-independent apoptosis) and staurosporine (STS, a protein kinase inhibitor)-induced apoptosis. AIF knockdown reduced STS-induced apoptosis in both of 16E6-expressing and 6E6-expressing cells; however, the reduction in 16E6-expressing cells was lower than that in 6E6-expressing cells. These findings indicate that 16E6, but not 6E6, blocks AIF-mediated apoptosis, and that AIF may represent a novel therapeutic target for HPV-induced cervical cancer.
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http://dx.doi.org/10.1038/s41598-020-71134-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450093PMC
August 2020

Genetic control of CCL24, POR, and IL23R contributes to the pathogenesis of sarcoidosis.

Commun Biol 2020 08 21;3(1):465. Epub 2020 Aug 21.

Department of Ophthalmology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.

Sarcoidosis is a genetically complex systemic inflammatory disease that affects multiple organs. We present a GWAS of a Japanese cohort (700 sarcoidosis cases and 886 controls) with replication in independent samples from Japan (931 cases and 1,042 controls) and the Czech Republic (265 cases and 264 controls). We identified three loci outside the HLA complex, CCL24, STYXL1-SRRM3, and C1orf141-IL23R, which showed genome-wide significant associations (P < 5.0 × 10) with sarcoidosis; CCL24 and STYXL1-SRRM3 were novel. The disease-risk alleles in CCL24 and IL23R were associated with reduced CCL24 and IL23R expression, respectively. The disease-risk allele in STYXL1-SRRM3 was associated with elevated POR expression. These results suggest that genetic control of CCL24, POR, and IL23R expression contribute to the pathogenesis of sarcoidosis. We speculate that the CCL24 risk allele might be involved in a polarized Th1 response in sarcoidosis, and that POR and IL23R risk alleles may lead to diminished host defense against sarcoidosis pathogens.
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http://dx.doi.org/10.1038/s42003-020-01185-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442816PMC
August 2020

A Comparison Between Monofocal and Multifocal Intraocular Lenses in the Influence of Pupil Dilation on Target Postoperative Refraction.

Asia Pac J Ophthalmol (Phila) 2020 Sep-Oct;9(5):420-425

Department of Ophthalmology, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan.

Purpose: The aim of this study was to compare the influence of pupil dilation on power calculation formulas for third- (Hoffer Q, SRK/T) and fourth- (Haigis, Holladay3) generation intraocular lens (IOL) between monofocal and multifocal IOLs.

Design: Retrospective, comparative study.

Methods: We analyzed 280 eyes (162 monofocal, 118 multifocal; mean patient age: 72.9 ± 7.7 years; 41.25% male). Anterior chamber depth (ACD) and lens thickness (LT) were measured. Predicted postoperative refraction (PPR) and recommended IOL power were calculated using third- and fourth-generation formulas pre- and post-dilation. We evaluated the mean absolute change (MAC) in PPR, change in recommended IOL power per formula, and mean change in ACD and LT between pre- and post-dilation, for both monofocal and multifocal IOLs.

Results: ACD and LT showed significant changes post-dilation. The MAC in PPR was significantly higher with fourth-generation formulas than that with third-generation formulas, for both IOLs, and more so for multifocal IOLs. For both IOLs, the PPR change correlated positively with ACD changes, but negatively with LT changes, for fourth-generation formulas. Multifocals correlated significantly stronger with LT than monofocals. When using fourth-generation formulas post-dilation, the recommended IOL power changed more frequently in multifocals than in monofocals, although not significantly.

Conclusions: Pupil dilation did not influence third-generation formula calculations for both IOL types, but did affect PPR and recommended IOL power when using fourth-generation formulas, and more so for multifocals. Considering pupil dilation effects on monofocal and multifocal parameters is vital for accurate IOL calculation.
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http://dx.doi.org/10.1097/APO.0000000000000310DOI Listing
August 2020

Keratoconus-susceptibility gene identification by corneal thickness genome-wide association study and artificial intelligence IBM Watson.

Commun Biol 2020 07 31;3(1):410. Epub 2020 Jul 31.

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Keratoconus is a common ocular disorder that causes progressive corneal thinning and is the leading indication for corneal transplantation. Central corneal thickness (CCT) is a highly heritable characteristic that is associated with keratoconus. In this two-stage genome-wide association study (GWAS) of CCT, we identified a locus for CCT, namely STON2 rs2371597 (P = 2.32 × 10), and confirmed a significant association between STON2 rs2371597 and keratoconus development (P = 0.041). Additionally, strong STON2 expression was observed in mouse corneal epithelial basal cells. We also identified SMAD3 rs12913547 as a susceptibility locus for keratoconus development using predictive analysis with IBM's Watson question answering computer system (P = 0.001). Further GWAS analyses combined with Watson could effectively reveal detailed pathways underlying keratoconus development.
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http://dx.doi.org/10.1038/s42003-020-01137-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395727PMC
July 2020

Influence of pupil dilation on the Barrett universal II (new generation), Haigis (4th generation), and SRK/T (3rd generation) intraocular lens calculation formulas: a retrospective study.

BMC Ophthalmol 2020 Jul 20;20(1):299. Epub 2020 Jul 20.

Department of Ophthalmology, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan.

Background: Despite the surge in the number of cataract surgeries, there is limited information available regarding the influence of pupil dilation on predicted postoperative refraction and its comparison with recommended various intraocular lens power calculated using the different parameters. We used three different IOL power calculation formulas: Barrett Universal II (Barrett) (5-variable formula), Haigis (3-variable formula), and SRK/T (2-variable formula), in order to investigate the potential effect of pupil dilation on the predicted postoperative refraction (PPR) and recommended intraocular lens (IOL) power calculation.

Methods: This retrospective study included 150 eyes. All variables were measured and calculated using a ZEISS IOL Master 700. The following variables were measured before and after dilation: anterior chamber depth (ACD), lens thickness (LT), white-to-white (WTW). PPR and recommended IOL power were calculated by Barrett, Haigis, and SRK/T IOL calculation formulas. The change in each variable before and after dilation, and the correlations between all changes were analyzed using the Wilcoxon signed-rank test and the Spearman's rank-order correlation test, respectively.

Results: The mean absolute change (MAC) in PPR before and after dilation was found to be highest in the Barrett formula. Significant differences were found between each MAC (P <  0.0001). Significant changes were observed before and after dilation in ACD and LT (P <  0.0001), but not in WTW. Using the Barrett and Haigis formulas, there was a significant positive correlation between the change in PPR and change in ACD (P <  0.0001), and a negative correlation between change in PPR and change in LT (P <  0.0001). The correlations were strongest with the Barret formula followed by the Haigis, particularly in terms of LT. Changes in PPR determined by the Barrett formula also demonstrated a significant positive correlation with changes in WTW (P = 0.022). The recommended IOL power determined using Barrett and Haigis changed before and after dilation in 23.3 and 19.3% cases respectively, while SRK/T showed no change.

Conclusions: In terms of PPR and recommended IOL power, pupil dilation influenced mostly the Barrett formula. Given the stronger correlation between the changes in PPR when using Barrett and the changes in ACD, LT, and WTW, changes in ACD, LT, and WTW significantly affect how dilation influences the Barrett formula. Determining how dilation influences each formula and other variables is key to improving the accuracy of IOL calculations.
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http://dx.doi.org/10.1186/s12886-020-01571-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372826PMC
July 2020

Variants in IL23R-C1orf141 and ADO-ZNF365-EGR2 are associated with susceptibility to Vogt-Koyanagi-Harada disease in Japanese population.

PLoS One 2020 21;15(5):e0233464. Epub 2020 May 21.

Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.

Vogt-Koyanagi-Harada (VKH) disease is a systemic inflammatory disorder that affects pigment cell-containing organs such as the eye (e.g., chronic and/or recurrent granulomatous panuveitis). While the exact etiology and pathogenic mechanism of VKH disease are unclear, HLA-DR4 alleles have been documented to be strongly associated with VKH disease in various ethnic groups. Recently, a genome-wide association study (GWAS) found two new genetic risk factors (IL23R-C1orf141 and ADO-ZNF365-EGR2) in a non-HLA region from a Han Chinese population. In this study, we replicated these GWAS findings in a Japanese population. A total of 1,643 Japanese samples (380 cases with VKH disease and 1,263 healthy controls) were recruited. We assessed four single nucleotide polymorphisms (SNPs) shown in previous GWAS: rs78377598 and rs117633859 in IL23R-C1orf141, and rs442309 and rs224058 in ADO-ZNF365-EGR2. A significant allelic association with VKH disease was observed for all of the four SNPs (rs78377598: pc = 0.0057; rs117633859: pc = 0.0017; rs442309: pc = 0.021; rs224058: pc = 0.035). In genotypic association analysis, the minor alleles of IL23R-C1orf141 rs78377598 and rs117633859 had the strongest association with disease susceptibility under the additive model (pc = 0.0075 and pc = 0.0026, respectively). The minor alleles of ADO-ZNF365-EGR2 rs442309 and rs224058 were most strongly associated with disease susceptibility under the dominant model (pc = 0.00099 and pc = 0.0023, respectively). The meta-analysis of the current and previous studies found that all of the four SNPs exhibited a significantly strong association with VKH disease (meta-p < 0.00001: rs78377598, meta-odds ratio (OR) = 1.69; rs1176338, meta-OR = 1.82; rs442309, meta-OR = 1.34; rs224058, meta-OR = 1.33). In summary, our study replicated significant associations with VKH disease susceptibility reported in a previous GWAS. Thus, the IL23R-C1orf141 and ADO-ZNF365-EGR2 loci may play important roles in the development of VKH disease through genetic polymorphisms.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233464PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241744PMC
August 2020

Genome-Wide Association Study in Asians Identifies Novel Loci for High Myopia and Highlights a Nervous System Role in Its Pathogenesis.

Ophthalmology 2020 12 16;127(12):1612-1624. Epub 2020 May 16.

Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Japan; Department of Advanced Medicine for Ocular Diseases, Yokohama City University Graduate School of Medicine, Yokohama, Japan. Electronic address:

Purpose: To identify novel susceptibility loci for high myopia.

Design: Genome-wide association study (GWAS) followed by replication and meta-analysis.

Participants: A total of 14 096 samples from East and Southeast Asian populations (2549 patients with high myopia and 11 547 healthy controls).

Methods: We performed a GWAS in 3269 Japanese individuals (1668 with high myopia and 1601 control participants), followed by replication analysis in a total of 10 827 additional samples (881 with high myopia and 9946 control participants) from Japan, Singapore, and Taiwan. To confirm the biological role of the identified loci in the pathogenesis of high myopia, we performed functional annotation and Gene Ontology (GO) analyses.

Main Outcome Measures: We evaluated the association of single nucleotide polymorphisms with high myopia and GO terms enriched among genes identified in the current study.

Results: We identified 9 loci with genome-wide significance (P < 5.0 × 10). Three loci were previously reported myopia-related loci (ZC3H11B on 1q41, GJD2 on 15q14, and RASGRF1 on 15q25.1), and the other 6 were novel (HIVEP3 on 1p34.2, NFASC/CNTN2 on 1q32.1, CNTN4/CNTN6 on 3p26.3, FRMD4B on 3p14.1, LINC02418 on 12q24.33, and AKAP13 on 15q25.3). The GO analysis revealed a significant role of the nervous system related to synaptic signaling, neuronal development, and Ras/Rho signaling in the pathogenesis of high myopia.

Conclusions: The current study identified 6 novel loci associated with high myopia and demonstrated an important role of the nervous system in the disease pathogenesis. Our findings give new insight into the genetic factors underlying myopia, including high myopia, by connecting previous findings and allowing for a clarified interpretation of the cause and pathophysiologic features of myopia at the molecular level.
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http://dx.doi.org/10.1016/j.ophtha.2020.05.014DOI Listing
December 2020

Evidence-based diagnosis and clinical practice guidelines for intestinal Behçet's disease 2020 edited by Intractable Diseases, the Health and Labour Sciences Research Grants.

J Gastroenterol 2020 Jul 7;55(7):679-700. Epub 2020 May 7.

Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan.

Behçet's disease (BD) is an intractable systemic inflammatory disease characterized by four main symptoms: oral and genital ulcers and ocular and cutaneous involvement. The Japanese diagnostic criteria of BD classify intestinal BD as a specific disease type. Volcano-shaped ulcers in the ileocecum are a typical finding of intestinal BD, and punched-out ulcers can be observed in the intestine or esophagus. Tumor necrosis factor inhibitors were first approved for the treatment of intestinal BD in Japan and have been used as standard therapy. In 2007 and 2014, the Japan consensus statement for the diagnosis and management of intestinal BD was established. Recently, evidence-based JSBD (Japanese Society for BD) Clinical Practice Guidelines for BD (Japanese edition) were published, and the section on intestinal BD was planned to be published in English. Twenty-eight important clinical questions (CQs) for diagnosis (CQs 1-6), prognosis (CQ 7), monitoring and treatment goals (CQs 8-11), medical management and general statement (CQs 12-13), medical treatment (CQs 14-22), and surgical treatment (CQs 23-25) of BD and some specific situations (CQs 26-28) were selected as unified consensus by the members of committee. The statements and comments were made following a search of published scientific evidence. Subsequently, the levels of recommendation were evaluated based on clinical practice guidelines in the Medical Information Network Distribution Service. The degree of agreement was calculated using anonymous voting. We also determined algorithms for diagnostic and therapeutic approaches for intestinal BD. The present guidelines will facilitate decision making in clinical practice.
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http://dx.doi.org/10.1007/s00535-020-01690-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297851PMC
July 2020

ERAP1 polymorphisms interactions and their association with Behçet's disease susceptibly: Application of Model-Based Multifactor Dimension Reduction Algorithm (MB-MDR).

PLoS One 2020 5;15(2):e0227997. Epub 2020 Feb 5.

Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: Behçet's disease (BD) is a chronic multi-systemic vasculitis with a considerable prevalence in Asian countries. There are many genes associated with a higher risk of developing BD, one of which is endoplasmic reticulum aminopeptidase-1 (ERAP1). In this study, we aimed to investigate the interactions of ERAP1 single nucleotide polymorphisms (SNPs) using a novel data mining method called Model-based multifactor dimensionality reduction (MB-MDR).

Methods: We have included 748 BD patients and 776 healthy controls. A peripheral blood sample was collected, and eleven SNPs were assessed. Furthermore, we have applied the MB-MDR method to evaluate the interactions of ERAP1 gene polymorphisms.

Results: The TT genotype of rs1065407 had a synergistic effect on BD susceptibility, considering the significant main effect. In the second order of interactions, CC genotype of rs2287987 and GG genotype of rs1065407 had the most prominent synergistic effect (β = 12.74). The mentioned genotypes also had significant interactions with CC genotype of rs26653 and TT genotype of rs30187 in the third-order (β = 12.74 and β = 12.73, respectively).

Conclusion: To the best of our knowledge, this is the first study investigating the interaction of a particular gene's SNPs in BD patients by applying a novel data mining method. However, future studies investigating the interactions of various genes could clarify this issue.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227997PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001967PMC
April 2020

Common variants in the gene are associated with lattice degeneration of the retina in a Japanese population.

Mol Vis 2019 5;25:843-850. Epub 2019 Dec 5.

Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.

Purpose: Lattice degeneration of the retina is a vitreoretinal disorder characterized by a visible fundus lesion that predisposes the patient to retinal detachment. It has been suggested that collagen type II alpha 1 () gene variants may contribute to the development of disorders associated with retinal detachment. Here we investigated whether gene variants were associated with the risk of lattice degeneration of the retina.

Methods: We recruited 634 Japanese patients with lattice degeneration of the retina and 1694 Japanese healthy controls. We genotyped 13 tagging single-nucleotide polymorphisms (SNPs) in . We also performed imputation analysis to evaluate the potential association of un-genotyped SNPs, involving the imputation of 65 SNPs.

Results: Two intronic SNPs-rs1793954 and rs1635533-were significantly associated with lattice degeneration of the retina. The SNP rs1793954 showed the strongest association, with its C allele carrying an increased disease risk (p = 0.0016, corrected p = 0.021, OR = 1.25). The rs1793954 and rs1635533 SNPs were in strong linkage disequilibrium with each other ( = 0.99), and conditional analysis revealed that rs1793954 could account for the association between rs1635533 and the disease.

Conclusions: Our results suggested that gene variants may contribute to the development of lattice degeneration of the retina. Further genetic and functional analyses of COL2A1 variants are needed to clarify the present findings.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925665PMC
June 2020

Guidelines for the treatment of skin and mucosal lesions in Behçet's disease: A secondary publication.

J Dermatol 2020 Mar 6;47(3):223-235. Epub 2020 Jan 6.

Institute of Dermato-Immunology and Allergy, Southern Tohoku General Hospital, Koriyama, Japan.

In the current study, we present guidelines for the diagnosis and treatment of the mucocutaneous lesions of Behçet's disease, which is a chronic inflammatory disease characterized by the involvement of various organs, including mucocutaneous, ocular, vascular, intestinal and central nervous system lesions. It is often identified in the Middle East Mediterranean to East Asia region. Skin manifestations include erythema nodosum, papulopustular lesions and thrombophlebitis, and mucosal manifestations include oral and genital ulcers. These mucocutaneous lesions are characteristically the first signs of Behçet's disease and are important to be recognized for the early diagnosis of the disease. Moreover, these manifestations also recur and persist over the long-term course of the disease. The management of mucocutaneous lesions is important to prevent recurrence. We developed consensus guidelines that provide recommendations for general practitioners and dermatologists and physicians on the management of the mucocutaneous lesions of Behçet's disease.
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http://dx.doi.org/10.1111/1346-8138.15207DOI Listing
March 2020

Genome-wide association analyses identify two susceptibility loci for pachychoroid disease central serous chorioretinopathy.

Commun Biol 2019 12;2:468. Epub 2019 Dec 12.

Department of Ophthalmology, Donders Institute of Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands.

The recently emerged pachychoroid concept has changed the understanding of age-related macular degeneration (AMD), which is a major cause of blindness; recent studies attributed AMD in part to pachychoroid disease central serous chorioretinopathy (CSC), suggesting the importance of elucidating the CSC pathogenesis. Our large genome-wide association study followed by validation studies in three independent Japanese and European cohorts, consisting of 1546 CSC samples and 13,029 controls, identified two novel CSC susceptibility loci: and near (rs13278062, odds ratio = 1.35,  = 1.26 × 10; rs6061548, odds ratio = 1.63,  = 5.36 × 10). A T allele at rs13278062, a risk allele for CSC, is known to be a risk allele for AMD. This study not only identified new susceptibility genes for CSC, but also improves the understanding of the pathogenesis of AMD.
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http://dx.doi.org/10.1038/s42003-019-0712-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6908630PMC
July 2020