RESUMO
We aimed to determine the role of cathepsin S (CTSS) in modulating oxidative stress-induced immune and inflammatory reactions and angiogenesis in age-related macular degeneration. Human retinal pigment epithelium cells line ARPE-19 (immature) were maintained and treated with H2O2. The expression of CTSS, inflammatory cytokines, and complement factors induced by oxidative stress was compared between cells incubated without (control) and with CTSS knockdown (using small interfering ribonucleic acid; siRNA). To evaluate the role of CTSS in angiogenesis, we assayed tube formation using human umbilical vein endothelial cells and conditioned medium from ARPE-19 cells. We also used a mouse model of laser-induced choroidal neovascularization. CTSS levels were higher in ARPE-19 cells treated with H2O2 than in control cells. Oxidative stress-induced CTSS resulted in significantly elevated transcription of nuclear factor kappa B-dependent inflammatory cytokines, complement factors C3a and C5a, membrane attack complex (C5b-9), and C3a and C5a receptors. siRNA-mediated knockdown of CTSS reduced the number of inflammatory signals. Furthermore, oxidative stress-induced CTSS regulated the expression of peroxisome proliferator-activated receptor γ and vascular endothelial growth factor A/Akt serine/threonine kinase family signaling, which led to angiogenesis. Tube formation assays and mouse models of choroidal neovascularization revealed that CTSS knockdown ameliorated angiogenesis in vitro and in vivo. The present findings suggest that CTSS modulates the complement pathway, inflammatory reactions, and neovascularization, and that CTSS knockdown induces potent immunomodulatory effects. Hence, it could be a promising target for the prevention and treatment of early- and late-stage age-related macular degeneration.
Assuntos
Catepsinas , Neovascularização de Coroide , Modelos Animais de Doenças , Degeneração Macular , Estresse Oxidativo , Epitélio Pigmentado da Retina , Humanos , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Animais , Camundongos , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/genética , Neovascularização de Coroide/patologia , Catepsinas/metabolismo , Catepsinas/genética , Degeneração Macular/metabolismo , Degeneração Macular/genética , Degeneração Macular/patologia , Camundongos Endogâmicos C57BL , Western Blotting , Linhagem Celular , Citocinas/metabolismo , RNA Interferente Pequeno/genética , Células Endoteliais da Veia Umbilical Humana/metabolismoRESUMO
PURPOSE: To evaluate the changes in choriocapillaris vessel density (VD) in eyes with pachychoroid pigment epitheliopathy (PPE) using swept-source optical coherence tomography (OCT) angiography (OCTA). METHODS: This study included 83 eyes with PPE and 42 control eyes. We collected OCT and OCTA parameters, including central point thickness, subfoveal choroidal thickness (SFChT), and choriocapillaris VD of the fovea (CC fovea) and parafovea. The parafoveal area was divided into superior, nasal, inferior, and temporal choriocapillaris areas. Maximum (CC max) and minimum (CC min) choriocapillaris VD were defined as the highest and lowest values among the four parafoveal subfield VDs, respectively. We analyzed the average choriocapillaris VD, CC max, CC min, CC fovea, and the difference between CC max and CC min (CC delta) individually and compared all the parameters between PPE and control eyes. RESULTS: CC max (56.0% ± 1.7%) was significantly higher and CC min (50.9% ± 2.0%) significantly lower in eyes with PPE than in control eyes (CC max, 55.3% ± 1.0%, P = 0.006; CC min, 51.5% ± 1.3%, P = 0.046). The CC delta value (5.0% ± 2.1%) and SFChT (389.9 ± 129.9 µm) were also significantly higher in eyes with PPE than in the control group (3.7% ± 1.5%, P < 0.001; 268.2 ± 102.2 µm, P < 0.001; respectively). CONCLUSIONS: Choriocapillaris VD showed higher variability (hyperperfusion and hypoperfusion) in eyes with PPE than in control eyes. Choriocapillaris hypoperfusion may precede the development of PPE; however, choriocapillaris hyperperfusion is associated with projection artifacts.
Assuntos
Corioide , Tomografia de Coerência Óptica , Humanos , Angiofluoresceinografia/métodos , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , PerfusãoRESUMO
Hyperglycemia plays a key role in the development of microvascular complications, endothelial dysfunction (ED), and inflammation. It has been demonstrated that cathepsin S (CTSS) is activated in hyperglycemia and is involved in inducing the release of inflammatory cytokines. We hypothesized that blocking CTSS might alleviate the inflammatory responses and reduce the microvascular complications and angiogenesis in hyperglycemic conditions. In this study, we treated human umbilical vein endothelial cells (HUVECs) with high glucose (HG; 30 mM) to induce hyperglycemia and measured the expression of inflammatory cytokines. When treated with glucose, hyperosmolarity could be linked to cathepsin S expression; however, many have mentioned the high expression of CTSS. Thus, we made an effort to concentrate on the immunomodulatory role of the CTSS knockdown in high glucose conditions. We validated that the HG treatment upregulated the expression of inflammatory cytokines and CTSS in HUVEC. Further, siRNA treatment significantly downregulated CTSS expression along with inflammatory marker levels by inhibiting the nuclear factor-kappa B (NF-κB) mediated signaling pathway. In addition, CTSS silencing led to the decreased expression of vascular endothelial markers and downregulated angiogenic activity in HUVECs, which was confirmed by a tube formation experiment. Concurrently, siRNA treatment reduced the activation of complement proteins C3a and C5a in HUVECs under hyperglycemic conditions. These findings show that CTSS silencing significantly reduces hyperglycemia-induced vascular inflammation. Hence, CTSS may be a novel target for preventing diabetes-induced microvascular complications.
Assuntos
Complicações do Diabetes , Hiperglicemia , Humanos , NF-kappa B/metabolismo , Transdução de Sinais , Hiperglicemia/complicações , Hiperglicemia/genética , Hiperglicemia/metabolismo , Glucose/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Inflamação/genética , Inflamação/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Complicações do Diabetes/metabolismo , Citocinas/metabolismoRESUMO
PURPOSE: To evaluate the difference between the incidences of sterile endophthalmitis after administration of intravitreal aflibercept injection using two different types of syringes. METHODS: We administered a total of 498 intravitreal aflibercept injections between September 2017 and August 2021. The disposable syringe used was changed from a 1-mL disposable syringe (Profi syringe, Shinchang Medical., Ltd. Korea) to a 1-mL Becton Dickenson Luer-Lok syringe (BD, Franklin, NJ, USA) in September 2019. Thus, the patients who received injections before and after September 1, 2019, were classified into group 1 and group 2, respectively. The incidence of aflibercept-related sterile endophthalmitis between the two groups was compared. RESULTS: In group 1, six (2.791%) out of 215 cases were diagnosed with sterile endophthalmitis and prescribed topical or oral steroids. In group 2, one (0.353%) out of 283 cases was diagnosed with sterile endophthalmitis and prescribed a steroid eye drop. The incidence of sterile endophthalmitis was significantly different between the two groups (P = 0.046). CONCLUSION: The BD Luer-Lok syringe is associated with a lower incidence of aflibercept-related sterile endophthalmitis than the conventional polypropylene syringe. Differences in immunogenicity associated with silicone oil lubricants within the syringes might be one of the potential reasons behind the difference in the incidence of the sterile endophthalmitis.
Assuntos
Endoftalmite , Seringas , Inibidores da Angiogênese , Endoftalmite/diagnóstico , Endoftalmite/epidemiologia , Endoftalmite/etiologia , Humanos , Incidência , Injeções Intravítreas , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão , Estudos Retrospectivos , Seringas/efeitos adversosRESUMO
PURPOSE: To investigate the correlation of foveal photoreceptor integrity with the vessel density (VD) of the retina and choriocapillaris using swept source optical coherence tomography angiography in eyes with diabetic retinopathy. METHODS: We retrospectively reviewed subjects having eyes with diabetic retinopathy, who underwent optical coherence tomography angiography using swept source optical coherence tomography (DRI OCT Triton; Topcon). We analyzed the area of the foveal avascular zone and VDs of the superficial capillary plexus, deep capillary plexus, and choriocapillaris. The length of the lateral extent of ellipsoid zone disruption, central subfield thickness, and subfoveal choroidal thickness were measured. Furthermore, we analyzed factors that were closely associated with the length of ellipsoid zone disruption. RESULTS: A total of 159 eyes with diabetic retinopathy and 30 healthy control eyes were included in this study. In all eyes, the lengths of ellipsoid zone disruption were positively correlated with the foveal avascular zone area (P = 0.009). However, they were negatively correlated with the parafoveal VD of the superficial capillary plexus (P = 0.049), the foveal VD of deep capillary plexus (P = 0.003), and that of the choriocapillaris (P = 0.036). CONCLUSION: The size of the foveal avascular zone and ischemia at the deep capillary plexus may play an important role in maintaining foveal photoreceptor integrity in eyes with diabetic retinopathy. Considering optical coherence tomography angiography artifacts, such as projection and shadowing, future studies are required to reveal the correlation between ellipsoid zone disruption and the VD of the choriocapillaris.
Assuntos
Corioide/irrigação sanguínea , Retinopatia Diabética/fisiopatologia , Células Fotorreceptoras de Vertebrados/patologia , Vasos Retinianos/patologia , Idoso , Índice de Massa Corporal , Angiografia por Tomografia Computadorizada , Retinopatia Diabética/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia de Coerência ÓpticaRESUMO
OBJECTIVE: Aberrant neovascularization is a leading cause of blindness in several eye diseases, including age-related macular degeneration and proliferative diabetic retinopathy. The identification of key regulators of pathological ocular neovascularization has been a subject of extensive research and great therapeutic interest. Here, we explored the previously unrecognized role of cKIT and its ligand, SCF (stem cell factor), in the pathological ocular neovascularization process. Approach and Results: Compared with normoxia, hypoxia, a crucial driver of neovascularization, caused cKIT to be highly upregulated in endothelial cells, which significantly enhanced the angiogenic response of endothelial cells to SCF. In murine models of pathological ocular neovascularization, such as oxygen-induced retinopathy and laser-induced choroidal neovascularization models, cKIT and SCF expression was significantly increased in ocular tissues, and blockade of cKIT and SCF using cKit mutant mice and anti-SCF neutralizing IgG substantially suppressed pathological ocular neovascularization. Mechanistically, SCF/cKIT signaling induced neovascularization through phosphorylation of glycogen synthase kinase-3ß and enhancement of the nuclear translocation of ß-catenin and the transcription of ß-catenin target genes related to angiogenesis. Inhibition of ß-catenin-mediated transcription using chemical inhibitors blocked SCF-induced in vitro angiogenesis in hypoxia, and injection of a ß-catenin agonist into cKit mutant mice with oxygen-induced retinopathy significantly enhanced pathological neovascularization in the retina. Conclusions; Our data reveal that SCF and cKIT are promising novel therapeutic targets for treating vision-threatening ocular neovascular diseases.
Assuntos
Regulação da Expressão Gênica , Doenças Retinianas/genética , Doenças Retinianas/metabolismo , Neovascularização Retiniana/genética , Fator de Células-Tronco/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Análise de Variância , Inibidores da Angiogênese/farmacologia , Animais , Células Cultivadas , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Hipóxia/complicações , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-kit/genética , Doenças Retinianas/patologia , Doenças Retinianas/fisiopatologia , Transdução de Sinais/genéticaRESUMO
BACKGROUND: To assess the effect of pan-retinal photocoagulation (PRP) on choroidal vascular parameters in eyes with advanced diabetic retinopathy (DR). METHODS: Forty patients (65 eyes) with severe nonproliferative DR or proliferative DR who underwent PRP were included. Changes in choroidal vascular parameters were assessed at 3, 6, and 12 months after PRP by using swept-source optical coherence tomography (OCT) and OCT angiography and were compared with baseline values. RESULTS: Choroidal vascularity index (CVI) significantly decreased from 66.27% ± 1.55% at baseline to 65.85% ± 1.61%, 65.77% ± 1.29%, and 65.74% ± 1.60% at 3, 6, and 12 months after PRP, respectively. The ratio of luminal area to stromal area (L/S ratio) also significantly decreased from 1.98 ± 0.15 at baseline to 1.94 ± 0.14, 1.95 ± 0.13, and 1.93 ± 0.14 at 3, 6, and 12 months after PRP, respectively. The subfoveal choroidal thickness (SFCT) similarly showed a significant decrease from 319.50 ± 56.64 µm at baseline to 299. 07 ± 51.14 µm, 294.70 ± 58.96 µm, and 280.93 ± 53.57 µm at 3, 6, and 12 months after PRP, respectively. However, the choriocapillaris vessel density in both the fovea and parafovea showed no significant differences following PRP. CONCLUSION: Eyes with advanced DR showed a significant reduction in CVI, L/S ratio, and SFCT over 12 months after PRP treatment.
Assuntos
Corioide/irrigação sanguínea , Retinopatia Diabética/diagnóstico , Angiofluoresceinografia/métodos , Fotocoagulação a Laser/métodos , Vasos Retinianos/patologia , Tomografia de Coerência Óptica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Retinopatia Diabética/cirurgia , Feminino , Seguimentos , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
PURPOSE: To describe persistent remnants of dexamethasone intravitreal implant (DEX implant) and evaluate the risk factors for remnant persistence in patients who received a DEX implant. METHODS: This retrospective observational study involved a retrospective chart review of 133 eyes from 129 patients who received DEX implant injection. RESULTS: Seventeen eyes of 17 patients (12.78%) exhibited remnant persistence >1 year after DEX implant injection; eight eyes (13.33%) were diagnosed with branching retinal vein occlusion, three eyes (14.28%) were diagnosed with central retinal vein occlusion, and six eyes (35.3%) were diagnosed with diabetic macular edema. The number of intravitreal DEX implant injections and triamcinolone acetonide injections administered to eyes with remnant persistence was significantly higher than that administered to the eyes without remnant persistence (P < 0.001 and P = 0.024, respectively). Remnants caused symptomatic floaters in 11.7% (2/17 eyes) of the patients with remnants and in 1.5% (2/133) of the entire patient cohort. CONCLUSION: DEX implant was not completely dissolved in the eyes that received multiple DEX implant or triamcinolone acetonide injections.
Assuntos
Dexametasona/administração & dosagem , Implantes de Medicamento/efeitos adversos , Oftalmopatias/etiologia , Corpos Estranhos no Olho/etiologia , Glucocorticoides/administração & dosagem , Corpo Vítreo/patologia , Idoso , Retinopatia Diabética/tratamento farmacológico , Oftalmopatias/diagnóstico , Corpos Estranhos no Olho/diagnóstico , Feminino , Humanos , Pressão Intraocular/fisiologia , Injeções Intravítreas , Edema Macular/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Oclusão da Veia Retiniana/tratamento farmacológico , Estudos Retrospectivos , Acuidade Visual/fisiologiaRESUMO
BACKGROUND: To compare the effect of pan-retinal photocoagulation (PRP) using pattern scanning or conventional laser on subfoveal choroidal thickness (SFChT). METHODS: Thirty-eight patients (64 eyes) with advanced diabetic retinopathy (DR) who underwent PRP using pattern scanning or conventional laser were included. Changes in SFChT were compared with baseline values at 1, 3, 6, and 12 months after PRP using swept-source optical coherence tomography. RESULTS: The conventional laser group showed a statistically significant decrease in SFChT at 1, 3, 6, and 12 months after PRP (P < 0.001). SFChT was significantly decreased at 3 (P = 0.025), 6 (P = 0.004), and 12 (P < 0.001) months after treatment in the pattern laser group. CONCLUSION: Eyes with advanced DR showed a significant reduction in SFChT over 12 months regardless of the type of laser used; however, the reduction was sooner after conventional laser than after pattern laser.
Assuntos
Corioide/diagnóstico por imagem , Retinopatia Diabética/cirurgia , Angiofluoresceinografia/métodos , Fotocoagulação a Laser/métodos , Retina/cirurgia , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Adulto , Idoso , Retinopatia Diabética/diagnóstico , Feminino , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Retina/diagnóstico por imagem , Estudos RetrospectivosRESUMO
PURPOSE: To quantify the susceptibility of the deep capillary plexus (DCP) in comparison with that of the superficial capillary plexus (SCP) in eyes with branch retinal vein occlusion (BRVO) using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: SS-OCTA (TritonTM; Topcon, Tokyo, Japan) scans (3 × 3 mm) of 41 patients with BRVO were retrospectively analyzed. The mean vessel densities (VDs) of the SCP and the DCP were calculated in eyes with BRVO using the ImageJ program (National Institutes of Health, Bethesda, MD, USA) and compared with those in the normal fellow eye without any morbidity or unaffected sector in the BRVO eye. RESULTS: The reduction rate of mean VD in SCP and DCP between the affected and unaffected sector of eyes with BRVO was 13.88 and 24.60%, respectively. Additionally, the reduction rate of mean VD in the SCP and DCP in the affected sector of BRVO eyes versus the corresponding sector of fellow eyes was 13.31 and 24.49%, respectively. CONCLUSION: The DCP was 1.77-1.84 times more affected than the SCP by ischemic damage in eyes with BRVO.
Assuntos
Capilares/patologia , Angiofluoresceinografia/métodos , Oclusão da Veia Retiniana/diagnóstico , Veia Retiniana/patologia , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Idoso , Feminino , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Angiogenin (ANG) is involved in the innate immune system and inflammatory disease. The aim of this study is to evaluate the anti-inflammatory effects of ANG in an endotoxin induced uveitis (EIU) rat model and the pathways involved. EIU rats were treated with balanced salt solution (BSS), a non-functional mutant ANG (mANG), or wild-type ANG (ANG). The integrity of the blood-aqueous barrier was evaluated by the infiltrating cell and protein concentrations in aqueous humor. Histopathology, Western blot, and real-time qRT-PCR of aqueous humor and ocular tissue were performed to analyze inflammatory cytokines and transcription factors. EIU treated with ANG had decreased inflammatory cells and protein concentrations in the anterior chamber. Compared to BSS and mANG, ANG treatment showed reduced expression of IL-1ß, IL-8, TNF-α, and Myd88, while the expression of IL-4 and IL-10 was increased. Western blot of ANG treatment showed decreased expression of IL-6, inducible nitric oxide synthase (iNOS), IL-1ß, TNF-α, and phosphorylated NF-κB and increased expression of IL-10. In conclusion, ANG seems to reduce effectively immune mediated inflammation in the EIU rat model by reducing the expression of proinflammatory cytokines, while increasing the expression of anti-inflammatory cytokines through pathways related to NF-κB. Therefore, ANG shows potential for effectively suppressing immune-inflammatory responses in vivo.
Assuntos
Anti-Inflamatórios/uso terapêutico , Ribonuclease Pancreático/uso terapêutico , Uveíte/induzido quimicamente , Uveíte/tratamento farmacológico , Animais , Núcleo Celular/metabolismo , Citocinas/genética , Citocinas/metabolismo , Endotoxinas , Inflamação/tratamento farmacológico , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Masculino , Modelos Biológicos , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Transporte Proteico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Receptor 4 Toll-Like/metabolismoRESUMO
PURPOSE: The purpose of the study is to investigate the characteristics of choriocapillaris flow based on the underlying choroidal vasculature in fellow eyes with central serous chorioretinopathy (CSC). METHODS: We included 57 patients with CSC and normal controls. Characteristics of choriocapillaris flow were evaluated using swept-source optical coherence tomography (OCT) angiography. We divided the choroidal layer into the vascular and stromal beds according to the choroid vessels on en-face OCT images. We compared the flow void area and mean vascular density of the choriocapillaris according to the underlying choroidal beds in the CSC and control group. RESULTS: The mean vascular density of the choriocapillaris in the CSC group was not different from that of the control group (P = 0.289). The flow void area was more frequently found in the CSC group (59.6%) than in the control group (29.8%, P = 0.002). The presence of the flow void area in the CSC group was associated with greater macular choroidal thickness (P = 0.004). In the CSC group, the mean flow void area and ratio of the choriocapillaris over the vascular bed were larger than those over the stromal bed (all P < 0.001). CONCLUSIONS: The location of the flow void area of the choriocapillaris was associated with the distribution of the underlying choroidal vessels. This suggests that the underlying choroidal vessels may affect choriocapillaris perfusion in pachychoroid eyes.
Assuntos
Capilares/fisiopatologia , Coriorretinopatia Serosa Central/diagnóstico , Corioide/irrigação sanguínea , Angiofluoresceinografia/métodos , Microcirculação/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Tomografia de Coerência Óptica/métodos , Doença Aguda , Adulto , Capilares/patologia , Coriorretinopatia Serosa Central/fisiopatologia , Feminino , Seguimentos , Fundo de Olho , Humanos , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Acuidade VisualRESUMO
PURPOSE: To present characteristics of choriocapillaris layer imaging with swept-source optical coherence tomography angiography (SS-OCTA) in eyes with macular hole (MH). METHODS: Patients with MH were included. Vascular density of choriocapillaris (VDC) and central flow void areas were obtained using SS-OCTA. Data were compared with age- and gender-matched normal controls. RESULTS: Fifty-one patients with MH and 51 controls were included. Among the 51 patients with MH, 19 had lamellar MH (LMH) and 32 had full-thickness MH (FTMH). While VDC in LMH (79.26 ± 4.06%) was not significantly different from that seen in fellow eyes (79.88 ± 4.28%, P = 0.729) and normal controls (80.53 ± 4.21%, P = 1.000), VDC in surgically closed FTMH (74.60 ± 7.37%) was similar to that of fellow eyes (75.45 ± 7.39%, P = 0.400) but lower than that of controls (78.37 ± 7.13%, P = 0.011). On univariate analysis of 32 patients with unilateral sealed FTMH, VDC was not correlated with basal hole area (P = 0.797) or preoperative area of disrupted ellipsoid zone (P = 0.863). Central flow void was detected in 32 eyes. Mean central flow void area was 0.82 ± 0.84 mm2, which correlated with preoperative area of disrupted ellipsoid zone (P = 0.001). CONCLUSIONS: Choriocapillaris layer imaging using SS-OCTA showed that choriocapillaris in both eyes of patients with unilateral FTMH had different characteristics from eyes with LMH or normal controls. These results suggest that variation in choriocapillaris layer flow is involved in the pathogenesis of MH.
Assuntos
Capilares/patologia , Corioide/irrigação sanguínea , Angiofluoresceinografia/métodos , Perfurações Retinianas/diagnóstico , Vasos Retinianos/patologia , Tomografia de Coerência Óptica/métodos , Feminino , Humanos , Macula Lutea/patologia , Masculino , Pessoa de Meia-Idade , Perfurações Retinianas/cirurgia , Estudos Retrospectivos , Acuidade Visual , Vitrectomia/métodosRESUMO
OBJECTIVE: Vascular smooth muscle cells (VSMCs) modulate their phenotype between synthetic and contractile states in response to environmental changes; this modulation plays a crucial role in the pathogenesis of restenosis and atherosclerosis. Here, we identified fibroblast growth factor 12 (FGF12) as a novel key regulator of the VSMC phenotype switch. APPROACH AND RESULTS: Using murine models and human specimens, we found that FGF12 was highly expressed in contractile VSMCs of normal vessel walls but was downregulated in synthetic VSMCs from injured and atherosclerotic vessels. In human VSMCs, FGF12 expression was inhibited at the transcriptional level by platelet-derived growth factor-BB. Gain- and loss-of-function experiments showed that FGF12 was both necessary and sufficient for inducing and maintaining the quiescent and contractile phenotypes of VSMCs. FGF12 inhibited cell proliferation through the p53 pathway and upregulated the key factors involved in VSMC lineage differentiation, such as myocardin and serum response factor. Such FGF12-induced phenotypic change was mediated by the p38 MAPK (mitogen-activated protein kinase) pathway. Moreover, FGF12 promoted the differentiation of mouse embryonic stem cells and the transdifferentiation of human dermal fibroblasts into SMC-like cells. Furthermore, adenoviral infection of FGF12 substantially decreased neointima hyperplasia in a rat carotid artery injury model. CONCLUSIONS: In general, FGF family members induce a synthetic VSMC phenotype. Interestingly, the present study showed the unanticipated finding that FGF12 belonging to FGF family, strongly induced the quiescent and contractile VSMC phenotypes and directly promoted VSMC lineage differentiation. These novel findings suggested that FGF12 could be a new therapeutic target for treating restenosis and atherosclerosis.
Assuntos
Doenças das Artérias Carótidas/metabolismo , Lesões das Artérias Carótidas/metabolismo , Diferenciação Celular , Plasticidade Celular , Fatores de Crescimento de Fibroblastos/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Regiões 5' não Traduzidas , Animais , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Becaplermina , Sítios de Ligação , Doenças das Artérias Carótidas/patologia , Lesões das Artérias Carótidas/genética , Lesões das Artérias Carótidas/patologia , Artéria Carótida Primitiva/metabolismo , Artéria Carótida Primitiva/patologia , Diferenciação Celular/efeitos dos fármacos , Linhagem da Célula , Plasticidade Celular/efeitos dos fármacos , Proliferação de Células , Células Cultivadas , Modelos Animais de Doenças , Células-Tronco Embrionárias/metabolismo , Fatores de Crescimento de Fibroblastos/genética , Genótipo , Humanos , Hiperplasia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia , Neointima , Fenótipo , Fosfatidilinositol 3-Quinase/metabolismo , Ligação Proteica , Proteínas Proto-Oncogênicas c-sis/farmacologia , Interferência de RNA , Ratos Sprague-Dawley , Transdução de Sinais , Transcrição Gênica , Transfecção , Vasoconstrição , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
PURPOSE: The purpose of our study was to investigate characteristics of retinal vessels in eyes with surgically closed macular holes (MH). METHODS: We included patients who underwent surgery for idiopathic MH and a follow-up examination using optical coherence tomography angiography (OCTA). The area of the foveal avascular zone (FAZ) and retinal vascular densities of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were calculated on the postoperative OCTA images and compared with those of age-matched normal controls. RESULTS: Twenty-eight patients with MH and 28 controls were included. Mean postoperative FAZ areas of SCP and DCP (0.317 ± 0.129 mm2 and 0.500 ± 0.174 mm2) were smaller than those of normal controls (0.406 ± 0.131 mm2 and 0.687 ± 0.147 mm2) (P = 0.013 and P < 0.001, respectively). Retinal vascular densities of SCP and DCP in the MH group (32.23 ± 1.45% and 31.85 ± 1.28%) were lower than those of the control group (33.26 ± 1.71% and 33.18 ± 1.89%) (P = 0.019 and P = 0.003, respectively). The retinal vascular densities of SCP and DCP were associated with postoperative mean ganglion cell-inner plexiform layer (GC-IPL) thickness (P = 0.033 and P = 0.035, respectively). The vascular densities were horizontally asymmetric and related to asymmetric distribution of GC-IPL thickness in the MH group. CONCLUSIONS: Surgically closed MH eyes had remodeled retinal vascular patterns, which were related to morphologic changes in the inner retinal layer. The healing process after MH surgery may be involved in asymmetric change in anatomy and hemodynamics of the inner retina.
Assuntos
Angiofluoresceinografia/métodos , Fóvea Central/irrigação sanguínea , Macula Lutea/patologia , Perfurações Retinianas/diagnóstico , Vasos Retinianos/diagnóstico por imagem , Acuidade Visual , Vitrectomia/métodos , Idoso , Capilares/patologia , Feminino , Fundo de Olho , Humanos , Masculino , Período Pós-Operatório , Perfurações Retinianas/cirurgia , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodosRESUMO
PURPOSE: The purpose was to investigate the effects of orbital decompression surgery on postoperative changes in interpupillary distance (IPD) and angle kappa in patients with thyroid-associated orbitopathy (TAO). METHODS: In patients with TAO who underwent orbital decompression surgery between January 1, 2014 and February 21, 2016, we measured exopthalmometry, IPD, inner intercanthal distance (IICD) and outer intercanthal distance (OICD) using a computer software program and angle kappa with an ORB scan II. We then analyzed preoperative and 3-month postoperative exophthalmometry, IPD, IICD, OICD and angle kappa to evaluate changes in eye position or rotation of the eyeball following orbital decompression surgery. RESULTS: Fifty-four patients (35 women and 19 men) with a mean age of 34.59 (range, 16-64 years) were enrolled in this study. After decompression surgery, the IPD was significantly decreased by 1.76 mm (preoperative, 63.14 ± 3.93 mm; postoperative, 61.38 ± 3.84 mm; P < 0.001), but angle kappa, IICD, and OICD did not vary significantly (P = 0.814, P = 0.635 and P = 0.092, respectively). CONCLUSIONS: A significant decrease in IPD was noted after orbital decompression in patients with TAO. However, there was no significant change in angle kappa. Therefore, the mechanism of change in the IPD is not an inward rotation of the eyeball, but rather an actual dorsal shift causing a wedging of the eye position itself within the orbit.
Assuntos
Descompressão Cirúrgica/métodos , Oftalmopatia de Graves/cirurgia , Iris/anatomia & histologia , Órbita/cirurgia , Adolescente , Adulto , Feminino , Seguimentos , Oftalmopatia de Graves/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
The aim of this study was to investigate the acute effects of ethanol administration on pattern-reversal visual evoked potential (VEP) and multifocal electroretinography (mfERG). Fifteen healthy subjects with no ocular or general disease were recruited. VEP (0.25° pattern sizes) and mfERG with 19 elements in two recording segments were performed before ethanol administration to obtain baseline for each participant. A few days later, the participants visited again for VEP and mfERG measurements after ethanol administration. Ethanol (0.75 g/kg) was administered orally over the course of 30 minutes. VEP and blood alcohol concentration were evaluated one hour after ethanol administration, and mfERG was conducted after pupil dilation. The Wilcoxon signed-rank test was used to compare parameter changes after randomized eye selection. The mean blood alcohol concentration was 0.034% ± 0.05% by volume. VEP revealed a P100 latency delay (109.4 ± 5.3; 113.1 ± 8.2; P = 0.008) after alcohol administration. The P1 implicit time of ring 1 on mfERG showed a trend of shortening after alcohol administration (37.9 ± 1.0; 37.2 ± 1.5; P = 0.048). However, the changes did not show statistical significance after Bonferroni correction. In conclusion, orally administrated ethanol (0.75 g/kg) appears to suppress the central nervous system, but it is not clear whether alcohol intake affects the retina.
Assuntos
Consumo de Bebidas Alcoólicas , Potenciais Evocados Visuais/fisiologia , Adulto , Eletrorretinografia , Feminino , Humanos , Masculino , Retina/fisiologiaRESUMO
PURPOSE: A pericentral pattern of hydroxychloroquine (HCQ) retinopathy recently has been recognized in the United States in patients of Asian heritage. We report on an investigation of this pericentral retinopathy within a Korean population. DESIGN: Retrospective, observational study. PARTICIPANTS: Patients taking HCQ who were referred to ophthalmology for screening of HCQ retinopathy. METHODS: The medical records of patients were reviewed, including spectral domain optical coherence tomography, fundus autofluorescence, and visual fields. MAIN OUTCOME MEASURES: Frequency of pericentral pattern of HCQ retinopathy and features of progression. RESULTS: Among 218 patients referred, 9 (4.1%) were diagnosed with toxicity. Of these, 8 had a predominantly pericentral pattern of retinal change, whereas only 1 had the classic parafoveal distribution of retinal damage. Progression of retinopathy was documented in 3 patients followed more than 12 months while taking HCQ. No progression was seen in 2 patients without retinal pigment epithelial (RPE) damage who were followed for at least 12 months after discontinuation of HCQ. CONCLUSIONS: We found that a pericentral pattern of HCQ retinopathy was predominant among Korean patients, rather than the traditional (bull's eye) parafoveal pattern of damage. Retinopathy progressed while on the drug, but the progression stopped in patients with toxicity detected before RPE damage. These observations suggest the need for new approaches when screening for HCQ toxicity in Asian patients.
Assuntos
Antirreumáticos/efeitos adversos , Hidroxicloroquina/efeitos adversos , Doenças Retinianas/induzido quimicamente , Adulto , Idoso , Povo Asiático/etnologia , Progressão da Doença , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Doenças Retinianas/diagnóstico , Doenças Retinianas/etnologia , Estudos Retrospectivos , Doenças Reumáticas/tratamento farmacológico , Tomografia de Coerência Óptica , Seleção Visual , Testes de Campo Visual , Campos Visuais/fisiologiaRESUMO
PURPOSE: To compare the lesion characteristics of two different types of confocal scanning laser ophthalmoscopy (cSLO) autofluorescence (AF) images in central serous chorioretinopathy (CSC). METHODS: The study included 63 eyes of 61 patients; 63 pairs of fundus autofluorescence (FAF) images were compared before CSC resolution in 63 eyes, FAF images of 31 eyes were also compared after CSC resolution. The lesion characteristics (brightness and composite pattern) were compared between Heidelberg Retina Angiograph 2 (HRA2; Heidelberg Engineering, Germany) and Optomap Tx (Optomap; Optos, Scotland) FAF images. The lesion composite pattern was categorized as diffuse or granular. Diffuse AF was defined as homogenously increased or decreased AF, and granular AF was defined as dot-like, coarse changes in AF. The mean disease duration and subretinal fluid (SRF) height in the spectral domain optical coherence tomography were compared according to the FAF image characteristics. RESULTS: Lesion brightness before CSC resolution was hypo-AF in 48 eyes (76.2 %), hyper-AF in three (4.8 %), and mixed-AF in 12 (19.0 %) in HRA2 FAF images. In comparison, nine (14.3 %) images were hypo-AF, 44 (69.8 %) were hyper-AF, and 10 (15.9 %) were mixed-AF in Optomap FAF images (P < 0.0001). There was no significant difference in lesion composite pattern between the two FAF image wavelengths. Patients with lesions that were hyper-AF in Optomap FAF and hypo-AF in HRA2 FAF had a shorter disease duration and greater SRF height (1 month, 281 um) than those who were hyper-AF in both Optomap and HRA2 images (26 months, 153 um; P = 0.004, 0.001). CONCLUSIONS: The two types of FAF images of CSC showed different lesion brightness before and after CSC resolution but demonstrated similar lesion composite patterns.
Assuntos
Coriorretinopatia Serosa Central/diagnóstico , Angiofluoresceinografia , Oftalmoscópios , Oftalmoscopia , Adulto , Coriorretinopatia Serosa Central/terapia , Corantes/administração & dosagem , Feminino , Fundo de Olho , Humanos , Verde de Indocianina/administração & dosagem , Fotocoagulação a Laser , Degeneração Macular , Masculino , Pessoa de Meia-Idade , Imagem Óptica , Fotoquimioterapia , Epitélio Pigmentado da Retina , Estudos Retrospectivos , Tomografia de Coerência ÓpticaRESUMO
PURPOSE: To investigate foveal inner retinal layer (IRL) restoration and its relationship with functional visual outcomes after membrane peeling in eyes with idiopathic epiretinal membrane (ERM) with foveal central thick IRL. METHODS: Consecutive eyes (n = 57) with a thick foveal IRL that underwent 25-gauge vitrectomy for ERM treatment were included. Complete ophthalmic and spectral domain optical coherence tomography examinations were performed before and 1 year after surgery. RESULTS: Before surgery, mean best-corrected visual acuity (BCVA) was 20/48 (logMAR, 0.38); central foveal thickness, 515.0 ± 90.9 µm; and central IRL thickness (CIRLT) at the fovea, 167.7 ± 80.1 µm. One year after ERM peeling, mean BCVA improved to 20/30 (logMAR, 0.18), central foveal thickness to 404.1 ± 96.4 µm, and CIRLT to 76.8 ± 68.0 µm. In multivariate analysis, initial BCVA and CIRLT at baseline correlated well with final BCVA and BCVA improvement at 12 months. In comparison with Group B eyes (persistently thick foveal IRL at 12 months), Group A eyes (restored foveal IRL at 12 months) had thinner CIRLT at baseline and showed a significant post-surgical improvement in BCVA and metamorphopsia. CONCLUSION: In eyes with idiopathic ERM and decreased vision due to abnormally thick IRL in the foveal center, postoperative visual outcomes correlated well with preoperative CIRLT and postoperative restoration of IRL configuration after ERM peeling.