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BACKGROUND: As gene-specific therapy for inherited retinal dystrophy (IRD) advances, unified variant interpretation across institutes is becoming increasingly important. This study aims to update the genetic findings of 86 retinitis pigmentosa (RP)-related genes in a large number of Japanese patients with RP by applying the standardised variant interpretation guidelines for Japanese patients with IRD (J-IRD-VI guidelines) built upon the American College of Medical Genetics and Genomics and the Association for Molecular Pathology rules, and assess the contribution of these genes in RP-allied diseases. METHODS: We assessed 2325 probands with RP (n=2155, including n=1204 sequenced previously with the same sequencing panel) and allied diseases (n=170, newly analysed), including Usher syndrome, Leber congenital amaurosis and cone-rod dystrophy (CRD). Target sequencing using a panel of 86 genes was performed. The variants were interpreted according to the J-IRD-VI guidelines. RESULTS: A total of 3564 variants were detected, of which 524 variants were interpreted as pathogenic or likely pathogenic. Among these 524 variants, 280 (53.4%) had been either undetected or interpreted as variants of unknown significance or benign variants in our earlier study of 1204 patients with RP. This led to a genetic diagnostic rate in 38.6% of patients with RP, with EYS accounting for 46.7% of the genetically solved patients, showing a 9% increase in diagnostic rate from our earlier study. The genetic diagnostic rate for patients with CRD was 28.2%, with RP-related genes significantly contributing over other allied diseases. CONCLUSION: A large-scale genetic analysis using the J-IRD-VI guidelines highlighted the population-specific genetic findings for Japanese patients with IRD; these findings serve as a foundation for the clinical application of gene-specific therapies.
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Retinose Pigmentar , Feminino , Humanos , Masculino , Distrofias de Cones e Bastonetes/genética , Distrofias de Cones e Bastonetes/patologia , População do Leste Asiático/genética , Predisposição Genética para Doença , Variação Genética , Japão , Amaurose Congênita de Leber/genética , Amaurose Congênita de Leber/patologia , Mutação , Retinose Pigmentar/genética , Retinose Pigmentar/patologia , Síndromes de Usher/genéticaRESUMO
PURPOSE: To report the efficacy of anti-tumor necrosis factor α (anti-TNFα) on autoimmune-mediated macular cone dysfunction in a Japanese woman with ulcerative colitis (UC). OBSERVATIONS: A 41-year-old woman presented with bilateral visual acuity loss and photophobia. She suffered from UC, and had been treated with prednisolone and 5-aminosalicylate since age 37. Although fundus photographs and optic coherence tomography images were unremarkable, electroretinograms (ERGs) were abnormal. A full-field electroretinogram (full-field ERG) revealed mildly decreased cone responses and oscillatory potential responses bilaterally. Importantly, focal-macular ERG (fmERG) and a multifocal electroretinogram (mfERG) revealed severe macular cone dysfunction in both eyes. Infliximab, a chimeric monoclonal anti-TNFα antibody, was administrated to treat recurrent abdominal symptoms and continued at 8-week intervals. Almost 6 months after infliximab therapy, the mfERG response (especially in the central retina), the fmERG response, and visual acuity recovered bilaterally. Abdominal symptoms also improved after infliximab therapy. CONCLUSIONS AND IMPORTANCE: Bilateral cone dysfunction with normal fundus were observed in a UC patient, resulting in loss of visual acuity and photophobia. This retinopathy may have been caused by an autoimmune mechanism, such as an autoimmune retinopathy or acute zonal occult outer retinopathy, which is most identifiable by ERG changes. This is the first report demonstrating the efficacy of infliximab in autoimmune retinal dysfunction.
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The coronavirus disease 2019 (COVID-19) pandemic is disturbing and overwhelming a regular medical care in the world. We evaluated the clinical characteristics of patients with primary rhegmatogenous retinal detachment (RRD) during the state of emergency for COVID-19 pandemic in Japan. We also reviewed measures against the COVID-19 pandemic in our institute with a focus on RRD treatment. Retrospectively, patients who underwent initial RRD surgery during the state of emergency between April 7, 2020 and May 25, 2020 were included. For comparison, we recruited patients who underwent surgery for initial RRD during the same period in the last 2 years (2018 and 2019). Data related to the number of surgeries, age, gender, macular detachment, proliferative vitreoretinopathy (PVR), preoperative visual acuity, surgical techniques, the time between the onset and hospitalization and/or surgery of the 2020 cohort were analyzed and compared with those of the 2018 and 2019 cohorts. Furthermore, we reviewed measures taken against COVID-19 in our institute. The number of RRD patients during the state of emergency tended to be lower than that within the last 2 years. Relatively lesser female (vs. male) patients were observed in the 2020 cohort than in the last 2 years (P = 0.084). In contrast, among all cohorts, no significant differences were observed in the incidence of macula-off and PVR, preoperative visual acuity, and the time period between symptom onset and hospitalization and/or surgery. This is the first report to show the clinical patterns of RRD during COVID-19 pandemic in Japan. Despite the state of emergency for the COVID-19 pandemic, no delay in the patient's initial visit to the hospital and surgery was observed. Further studies, including multicenter researches, are important for investigating the influence of COVID-19 on urgent ocular diseases.
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COVID-19/epidemiologia , Pandemias , Descolamento Retiniano/epidemiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tóquio/epidemiologiaRESUMO
Macular pucker, also known as an epiretinal membrane, sometimes forms after surgical repair of a rhegmatogenous retinal detachment (RRD) and can decrease visual acuity and cause aniseikonia. However, few reports are evaluating the risk factors of macular pucker using multivariate analysis. To evaluate the risk factors for macular pucker after RRD surgery, 226 patients who underwent RRD surgery and were monitored for greater than 12 months (23.2 ± 6.4 months) after surgery were analyzed retrospectively. Of these cases, macular pucker developed in 26 cases. Multiple logistic regression models of 22 clinical characteristics were performed. An increased risk of macular pucker after RRD surgery was significantly associated with preoperative vitreous haemorrhage (Odds ratio (OR), 4.71; 95% CI 1.19-18.62), multiple retinal breaks (OR, 8.07; 95% CI 2.35-27.71), re-detachment (OR, 19.66; 95% CI 4.87-79.38), and retinal detachment area (OR, 12.91; 95% CI 2.34-71.19). Macular pucker was not associated with the surgical technique. Regardless of the surgical technique used, careful observation for postoperative macular pucker is needed after RRD surgery in high-risk cases. These findings can be used to improve the surgical management of patients with RRD. (183 words).
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Membrana Epirretiniana/etiologia , Descolamento Retiniano/cirurgia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Descolamento Retiniano/patologia , Estudos Retrospectivos , Fatores de Risco , Recurvamento da Esclera/efeitos adversos , Hemorragia Vítrea/complicaçõesRESUMO
PRECIS: Malposition of the tube through the ciliary sulcus is more frequently observed with the Ahmed glaucoma valve (AGV) than the Baerveldt drainage implant (BDI) due to the weaker rigidity of the Ahmed tube. PURPOSE: To report intraoperative and early postoperative complications of ciliary sulcus tube insertion of glaucoma drainage implants (GDIs). PATIENTS AND METHODS: We performed retrospective analysis of 104 eyes of 94 patients with GDI tube insertion through the ciliary sulcus were performed. The rigidities of tubes were also examined using a microcompression tester. RESULTS: The mean observation period was 20.0 (range, 6 to 60) months. Thirteen eyes were treated with the BDI and 91 were with the AGV. The mean age of the patients was 69.3 (34 to 90) years. The mean intraocular pressure was 27.9 mm Hg before surgery and 12.9 mm Hg after surgery (P<0.01). Upon tube insertion 42/91 eyes (46%) with the AGV required reinsertion of the tube due to malpositioning, whereas only 1/13 (8%) eyes with BDI did (P<0.01). Transient hyphema (12 eyes) and hypotony (12 eyes) were observed as early postoperative complications with the AGV. Seven eyes with hypotony were treated by proline stenting of the tube. We could not accomplish sulcus insertions in 4 eyes. Microcompression analysis of the tubes showed that the BGI tube was more rigid than that of the AGV. CONCLUSIONS: Ciliary sulcus insertion of the tube is an effective method to control intraocular pressure. The tube of the AGV was more difficult to insert through the sulcus than the BDI due to its weaker rigidity.
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Implantes para Drenagem de Glaucoma , Pressão Intraocular , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Implantes para Drenagem de Glaucoma/efeitos adversos , Humanos , Complicações Pós-Operatórias , Implantação de Prótese , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Mouse models of allergic conjunctivitis mimic various aspects of human allergic conjunctivitis. They are useful as acute models of allergic conjunctivitis to study immunological aspects of this condition. In this chapter, we will describe ragweed-pollen-induced experimental allergic conjunctivitis (mostly driven by adaptive immunity), and papain-soaked contact lens-induced experimental allergic conjunctivitis (mostly driven by innate immunity). Giemsa staining of histological sections is used for quantification of the number of infiltrating eosinophils, which is useful to evaluate the severity of the allergic inflammation. Immunohistochemical staining and quantitative PCR are used to clarify spatiotemporal expression of proinflammatory molecules in the conjunctival tissue. Flow cytometric analysis of conjunctival tissue is used for the detection of innate lymphoid cell type 2 (ILC2) in the ocular surface tissues.
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Ambrosia/imunologia , Túnica Conjuntiva/efeitos dos fármacos , Conjuntivite Alérgica/imunologia , Modelos Animais de Doenças , Linfócitos/efeitos dos fármacos , Papaína/administração & dosagem , Imunidade Adaptativa/efeitos dos fármacos , Adjuvantes Imunológicos/administração & dosagem , Alérgenos/administração & dosagem , Hidróxido de Alumínio/administração & dosagem , Ambrosia/química , Animais , Biomarcadores/metabolismo , Túnica Conjuntiva/imunologia , Túnica Conjuntiva/patologia , Conjuntivite Alérgica/induzido quimicamente , Conjuntivite Alérgica/genética , Conjuntivite Alérgica/patologia , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Eosinófilos/patologia , Feminino , Citometria de Fluxo/métodos , Expressão Gênica , Imunidade Inata/efeitos dos fármacos , Imunoglobulina E/genética , Imunoglobulina E/imunologia , Interleucinas/genética , Interleucinas/imunologia , Linfócitos/imunologia , Linfócitos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Pólen/efeitos adversos , Pólen/imunologia , Reação em Cadeia da Polimerase em Tempo Real/métodosRESUMO
PURPOSE: To establish with negative electroretinogram (ERG) the clinical entity of eight patients with unilateral severe photophobia, essentially normal fundus, good visual acuity, and severe cone and rod dysfunction. STUDY DESIGN: Multicenter retrospective observation case series. METHODS: Comprehensive ophthalmologic examinations were performed, including best-corrected visual acuity (BCVA), full-field ERGs and multifocal ERGs (mfERGs), fundus photographs, and OCT. Systemic and genetic examinations were performed. RESULTS: The mean (± SD) age at the onset was 60.0 ± 8.4 years, and the six patients noticed severe photophobia in the affected eye in spite of almost normal fundus appearance and good BCVA. The dark-adapted bright flash ERGs in the affected eye had relatively well-preserved a-waves and depressed b-waves, i.e., a negative ERG. Cone ERGs and both b- and d-waves of the photopic long-duration ERGs were almost undetectable. Rod ERGs were severely reduced; however, only two patients complained of night blindness. In five patients, the mfERGs were extinguished in the periphery but preserved in the central retina, resulting in good BCVA. Electrophysiological findings indicated a severe diffuse dysfunction of the inner retina affecting bipolar cells of both ON- and OFF-pathways, and in five patients there was a reduction in the thickness of the inner nuclear layer. In seven patients the retinal arteries were attenuated. Anti-retinal antibodies were detected in the serum of two patients. No genetic causes were found. CONCLUSIONS: The common features in the eight patients with unilateral negative ERGs suggest a new disease entity of unilateral acute inner retinal layer dysfunction. In most patients, the only subjective complain was photophobia.
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Eletrorretinografia , Fotofobia , Humanos , Fotofobia/diagnóstico , Fotofobia/etiologia , Retina , Células Fotorreceptoras Retinianas Cones , Estudos Retrospectivos , Acuidade VisualRESUMO
To clarify the early alterations of gene expression using a mouse model of glaucoma filtration surgery, we carried out microarray expression analysis. Using BALB/c mice, a filtration surgery model was made by incision of the limbal conjunctiva, followed by the insertion of a 33G needle tip into the anterior chamber, and 11-0 nylon sutures. Subgroups of mice were treated intraoperatively with 0.4 mg/ml mitomycin-C (MMC). At day 3 after surgery the bleb was maintained. The bleb region tissue was sampled 3 days after the filtration surgery, and gene expression analysis was carried out using a mouse Agilent 8 × 60 K array. We found 755 hyperexpressed transcripts in the bleb region compared to control conjunctiva. The hyperexpressed transcripts included epithelial cell metaplasia-related (Il1b, Krt16, Sprr1b), inflammation-related (Ccl2, Il6) and wound healing-related (Lox, Timp1) genes. We also found downregulation of a goblet cell marker gene (Gp2) in the bleb conjunctiva. MMC treatment suppressed elastin (Eln) gene expression and enhanced keratinization-related gene expression (Krt1, Lor) in the bleb region. Our results suggest the importance of epithelial wound healing after filtration surgery, and this filtration surgery model will be a useful tool for further pathophysiological analysis.
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Cirurgia Filtrante/efeitos adversos , Glaucoma/cirurgia , Infecção da Ferida Cirúrgica/metabolismo , Transcriptoma , Animais , Antibacterianos/uso terapêutico , Túnica Conjuntiva/metabolismo , Túnica Conjuntiva/cirurgia , Cirurgia Filtrante/instrumentação , Camundongos , Camundongos Endogâmicos BALB C , Mitomicina/uso terapêutico , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/genéticaRESUMO
To prevent corneal endothelial cell loss, ciliary sulcus tube insertion is preferred for the pseudophakic eye. However, we sometimes encounter technical difficulties when inserting the tube through the sulcus. Even in cases in which we are able to insert a 23-G needle through the sulcus into the space between the iris and intraocular lens, the tube of Ahmed valve may stray into the vitreous cavity or under Elschnig pearls. To remedy such conditions, we developed a new tube insertion method using a 4-0 proline stent as a guide to insert the tube in the appropriate position.
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Implantes para Drenagem de Glaucoma , Glaucoma/cirurgia , Prolina , Implantação de Prótese/métodos , Suturas , Perda de Células Endoteliais da Córnea/prevenção & controle , Humanos , Pressão Intraocular , Stents , Técnicas de SuturaRESUMO
Leukotriene B4 (LTB4) is an inflammatory lipid mediator produced from arachidonic acid by multiple reactions catalyzed by two enzymes 5-lipoxygenase (5-LOX) and LTA4 hydrolase (LTA4H). The two receptors for LTB4 have been identified: a high-affinity receptor, BLT1, and a low-affinity receptor, BLT2. Our group identified 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid (12-HHT) as a high-affinity BLT2 ligand. Numerous studies have revealed critical roles for LTB4 and its receptors in various systemic diseases. Recently, we also reported the roles of LTB4, BLT1 and BLT2 in the murine ophthalmic disease models of mice including cornea wound, allergic conjunctivitis, and age-related macular degeneration. Moreover, other groups revealed the evidence of the ocular function of LTB4. In the present review, we introduce the roles of LTB4 and its receptors both in ophthalmic diseases and systemic inflammatory diseases. LTB4 and its receptors are putative novel therapeutic targets for systemic and ophthalmic diseases.
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Oftalmopatias/metabolismo , Receptores do Leucotrieno B4/metabolismo , Animais , Olho/metabolismo , Humanos , Inflamação/metabolismo , Leucotrieno B4/metabolismoRESUMO
Diabetic retinopathy (DR) is a widespread vision-threatening disease, and neuroretinal abnormality should be considered as an important problem. Brain-derived neurotrophic factor (BDNF) has recently been considered as a possible treatment to prevent DR-induced neuroretinal damage, but how BDNF is upregulated in DR remains unclear. We found an increase in hydrogen peroxide (H2O2) in the vitreous of patients with DR. We confirmed that human retinal endothelial cells secreted H2O2 by high glucose, and H2O2 reduced cell viability of MIO-M1, Müller glia cell line, PC12D, and the neuronal cell line and lowered BDNF expression in MIO-M1, whereas BDNF administration recovered PC12D cell viability. Streptozocin-induced diabetic rats showed reduced BDNF, which is mainly expressed in the Müller glia cell. Oral intake of eicosapentaenoic acid ethyl ester (EPA-E) ameliorated BDNF reduction and oscillatory potentials (OPs) in electroretinography (ERG) in DR. Mass spectrometry revealed an increase in several EPA metabolites in the eyes of EPA-E-fed rats. In particular, an EPA metabolite, 18-hydroxyeicosapentaenoic acid (18-HEPE), induced BDNF upregulation in Müller glia cells and recovery of OPs in ERG. Our results indicated diabetes-induced oxidative stress attenuates neuroretinal function, but oral EPA-E intake prevents retinal neurodegeneration via BDNF in Müller glia cells by increasing 18-HEPE in the early stages of DR.
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Fator Neurotrófico Derivado do Encéfalo/farmacologia , Retinopatia Diabética/metabolismo , Ácido Eicosapentaenoico/farmacologia , Células Endoteliais/metabolismo , Células Ependimogliais/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Neurônios Retinianos/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Diabetes Mellitus Experimental/metabolismo , Eletrorretinografia , Células Endoteliais/efeitos dos fármacos , Células Ependimogliais/efeitos dos fármacos , Ácidos Graxos Ômega-3/farmacologia , Feminino , Humanos , Peróxido de Hidrogênio/metabolismo , Masculino , Estresse Oxidativo/fisiologia , Ratos , Ratos Sprague-Dawley , Neurônios Retinianos/efeitos dos fármacosRESUMO
PURPOSE OF REVIEW: Lipids are one of the most important constituents in our body. Advances of lipidomics are elucidating the new roles of various lipid molecules in allergic diseases. For example, some reports showed anti-inflammatory effects of omega-3 fatty acids (FAs), such as docosahexaenoic acid, eicosapentaenoic acid, and their metabolites, on allergic diseases. Here, we introduce the role of lipid mediators in allergic conjunctivitis mouse model. RECENT FINDINGS: Lipidomics using liquid chromatography-tandem mass spectrometry can profile numerous lipid molecules from small tissue samples such as conjunctival specimens. Lipidomics analysis showed that various inflammatory lipid mediators are produced in the conjunctival tissue of allergic conjunctivitis mouse model. Dietary omega-3 FAs reduced these inflammatory lipid mediators in the conjunctiva and alleviated allergic conjunctivitis symptoms in mouse models. In addition, the roles of specialized proresolving lipid mediators (SPMs) have been reported for allergic inflammation. SUMMARY: Lipid mediators have important roles for the pathophysiology of the allergic diseases including allergic conjunctivitis. Omega-3 FAs and SPMs are expected as new treatment tools for allergic conjunctivitis.
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Túnica Conjuntiva , Conjuntivite Alérgica , Ácidos Docosa-Hexaenoicos , Ácido Eicosapentaenoico , Animais , Túnica Conjuntiva/imunologia , Túnica Conjuntiva/patologia , Conjuntivite Alérgica/tratamento farmacológico , Conjuntivite Alérgica/imunologia , Conjuntivite Alérgica/patologia , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/imunologia , Ácidos Docosa-Hexaenoicos/uso terapêutico , Ácido Eicosapentaenoico/imunologia , Ácido Eicosapentaenoico/uso terapêutico , Humanos , Lipidômica , CamundongosRESUMO
BACKGROUND: The genetic profile of retinitis pigmentosa (RP) in East Asian populations has not been well characterised. Therefore, we conducted a large-scale sequencing study to investigate the genes and variants causing RP in a Japanese population. METHODS: A total of 1209 Japanese patients diagnosed with typical RP were enrolled. We performed deep resequencing of 83 known causative genes of RP using next-generation sequencing. We defined pathogenic variants as those that were putatively deleterious or registered as pathogenic in the Human Gene Mutation Database or ClinVar database and had a minor allele frequency in any ethnic population of ≤0.5% for recessive genes or ≤0.01% for dominant genes as determined using population-based databases. RESULTS: We successfully sequenced 1204 patients with RP and determined 200 pathogenic variants in 38 genes as the cause of RP in 356 patients (29.6%). Variants in six genes (EYS, USH2A, RP1L1, RHO, RP1 and RPGR) caused RP in 65.4% (233/356) of those patients. Among autosomal recessive genes, two known founder variants in EYS [p.(Ser1653fs) and p.(Tyr2935*)] and four East Asian-specific variants [p.(Gly2752Arg) in USH2A, p.(Arg658*) in RP1L1, p.(Gly2186Glu) in EYS and p.(Ile535Asn) in PDE6B] and p.(Cys934Trp) in USH2A were found in ≥10 patients. Among autosomal dominant genes, four pathogenic variants [p.(Pro347Leu) in RHO, p.(Arg872fs) in RP1, p.(Arg41Trp) in CRX and p.(Gly381fs) in PRPF31] were found in ≥4 patients, while these variants were unreported or extremely rare in both East Asian and non-East Asian population-based databases. CONCLUSIONS: East Asian-specific variants in causative genes were the major causes of RP in the Japanese population.
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Povo Asiático/genética , Retinose Pigmentar/genética , Síndromes de Usher/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Frequência do Gene , Variação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Mutação , Retinose Pigmentar/diagnóstico , Análise de Sequência de DNA , Síndromes de Usher/diagnóstico , Adulto JovemRESUMO
Allergic conjunctivitis (AC) is one of the most common ocular surface diseases in the world. In AC, T helper type 2 (Th2) immune responses play central roles in orchestrating inflammatory responses. However, the roles of lipid mediators in the onset and progression of AC remain to be fully explored. Although previous reports have shown the beneficial effects of supplementation of ω-3 fatty acids in asthma or atopic dermatitis, the underlying molecular mechanisms are poorly understood. In this study, a diet rich in ω-3 fatty acids alleviated AC symptoms in both early and late phases without affecting Th2 immune responses, but rather by altering the lipid mediator profiles. The ω-3 fatty acids completely suppressed scratching behavior toward the eyes, an allergic reaction provoked by itch. Although total serum IgE levels and the expression levels of Th2 cytokines and chemokines in the conjunctiva were not altered by ω-3 fatty acids, eosinophil infiltration into the conjunctiva was dramatically suppressed. The levels of ω-6-derived proinflammatory lipid mediators, including those with chemoattractant properties for eosinophils, were markedly reduced in the conjunctivae of ω-3 diet-fed mice. Dietary ω-3 fatty acids can alleviate a variety of symptoms of AC by altering the lipid mediator profile.-Hirakata, T., Lee, H.-C., Ohba, M., Saeki, K., Okuno, T., Murakami, A., Matsuda, A., Yokomizo, T. Dietary ω-3 fatty acids alter the lipid mediator profile and alleviate allergic conjunctivitis without modulating Th2 immune responses.
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Conjuntivite Alérgica/imunologia , Ácidos Graxos Ômega-3/imunologia , Lipídeos/imunologia , Células Th2/imunologia , Animais , Asma/imunologia , Quimiocinas/imunologia , Citocinas/imunologia , Dieta/métodos , Eicosanoides/imunologia , Eosinófilos/imunologia , Feminino , Imunoglobulina E/imunologia , Camundongos , Camundongos Endogâmicos BALB CAssuntos
Conjuntivite Alérgica/genética , Conjuntivite Alérgica/imunologia , Resistência a Medicamentos/genética , Ceratoconjuntivite/genética , Ceratoconjuntivite/imunologia , Adolescente , Idoso , Criança , Resistência a Medicamentos/imunologia , Feminino , Perfilação da Expressão Gênica , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Análise de Sequência de RNA , Tacrolimo/uso terapêutico , TranscriptomaRESUMO
BACKGROUND: To investigate the potential roles of periostin (POSTN), an extracellular matrix preferentially expressed in Th2-skewed conditions in the pathophysiology of allergic conjunctivitis. METHODS: The roles of POSTN in ragweed-induced experimental allergic conjunctivitis (RW-EAC) were evaluated using both POSTN-knockout (KO) and congenic BALB/c wild-type mice. Histological analysis was carried out to enumerate eosinophils/basophils in the conjunctival tissue. Th2 cytokine expression was evaluated by quantitative polymerase chain reaction (Q-PCR), and microarray analysis was performed to elucidate genes differentially expressed in POSTN-KO and wild-type mice in the RW-EAC model. RESULTS: Upregulation of POSTN expression and eosinophil infiltration was observed in subconjunctival tissue of RW-EAC in the wild-type mice. The number of infiltrating eosinophils in the conjunctivae of RW-EAC was diminished in POSTN-KO mice compared to wild-type mice. Q-PCR analysis of conjunctival tissue showed induction of Th2 cytokine (Ccl5, Il4, Il5, Il13) expression in the RW-EAC and attenuated Ccl5, Il4, Il13 mRNA expression in the conjunctivae of the RW-EAC using POSTN-KO mice. Microarray analysis and immunohistochemical analysis showed diminished basophil marker (Mcpt8) expression and reduced numbers of infiltrating basophils in the conjunctivae of RW-EAC in POSTN-KO mice. CONCLUSIONS: POSTN expression in conjunctival tissue plays an indispensable role in the late-phase reaction of the RW-EAC model by facilitating eosinophil/basophil infiltration and augmenting Th2 cytokine expression.
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Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/imunologia , Conjuntivite Alérgica/imunologia , Alérgenos , Ambrosia , Animais , Antígenos de Plantas , Basófilos/imunologia , Túnica Conjuntiva/imunologia , Citocinas/imunologia , Modelos Animais de Doenças , Eosinófilos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , PólenRESUMO
To quantitatively evaluate changes in the sub-retinal pigment epithelial (RPE) space and determine the association with recurrent neovascular age-related macular degeneration (AMD). Twenty-two eyes treated with intravitreal aflibercept for treatment-naïve neovascular AMD were studied retrospectively. The sub-RPE area, volume, and central retinal thickness (CRT) were evaluated 1 and 2 months after the loading phase using spectral-domain optical coherence tomography. Recurrence was defined as newly detected neovascular activity during the 6 months after the loading phase. In eyes with recurrent AMD, the sub-RPE area increased significantly (P = 0.036) from 1 to 2 months after the loading phase and the sub-RPE volume increased marginally (P = 0.06). Subgroup analysis showed significant (P = 0.008 and P = 0.016, respectively) increases in the sub-RPE area and volume in typical AMD. In eyes with no recurrence, no significant changes occurred in the two parameters. No significant CRT changes occurred in eyes with or without a recurrence. A quantitative analysis demonstrated an increased likelihood of the sub-RPE space shortly after the loading phase in eyes with recurrent AMD; no changes occurred in eyes without a recurrence. These early changes in the sub-RPE space could indicate disease activity and are valuable for predicting recurrences of neovascular AMD.
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Epitélio Pigmentado da Retina/patologia , Degeneração Macular Exsudativa/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Recidiva , Estudos RetrospectivosRESUMO
OBJECTIVE: To describe the 1-year efficacy of aflibercept in Japanese patients with age-related macular degeneration (AMD) who were resistant to ranibizumab treatment. DESIGN: Retrospective case series. PARTICIPANTS: Fourteen consecutive eyes of 14 patients with AMD were enrolled who had no substantial response or developed resistance to intravitreal ranibizumab injections. METHODS: All patients were subcategorized into one of two subtypes of AMD: seven patients with occult choroidal neovascularization (CNV) and seven with polypoidal choroidal vasculopathy (PCV). Serial intravitreal aflibercept (IVA) injections were administered. Comprehensive ophthalmic examinations, including optical coherence tomography, were conducted at baseline and at follow-up examinations at 1, 3, 6, and 12 months after the initial IVA injection. The best-corrected visual acuity converted to logarithm of the minimum angle of resolution (logMAR) and central macular thickness (CMT) at each follow-up visit were compared with the baseline values. The anatomic response was also assessed with absorption or reduction of fluid in the subretina or subretinal pigment epithelial space. RESULTS: The logMAR best-corrected visual acuity improved significantly at 3, 6, and 12 months in the total cohort: at 3 and 6 months in patients with occult CNV and at 3 and 12 months in patients with PCV. The CMT decreased significantly at all follow-up visits in the total cohort as well as in both subtypes, except for the CMT at 6 months in PCV patients. The anatomic improvement was also demonstrated in all cases, and pigment epithelial detachments tended to be resolved more rapidly in patients with PCV than in patients with occult CNV. CONCLUSION: Conversion to IVA was effective in patients with AMD resistant to ranibizumab, showing rapid morphologic improvement. The logMAR visual acuity was raised significantly within 12 months, and the clinical course of visual acuity improvement may differ according to the AMD subtypes.