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1.
Opt Lett ; 49(14): 3910-3913, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39008739

RESUMO

In order to reduce the power consumption of digital signal processing (DSP) in a coherent optical communication system, a low complexity equalization scheme in DSP flow of a 400 Gb/s DP-16QAM system has been proposed. This scheme is based on Fermat number transform (FNT), which sequentially performs static equalization (SE) and dynamic equalization (DE) in the transform domain. For different distances, the proposed scheme finds the optimal solution under the condition that transform length and data bit width are mutually restricted under different transmission distances while achieving low complexity and optimal performance. The experimental results show that the adopted transform-domain equalization (TrDE) scheme has much lower computational complexity than the traditional frequency-domain equalization (FDE) and time-domain equalization (TDE) nearly without any performance loss. In the 80, 160, and 240 km scenarios, the number of multiplier is reduced by more than 72%, and the advantage becomes more obvious as the transmission capacity increases.

2.
Heliyon ; 9(4): e15353, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37123981

RESUMO

There are a large number of solutions for big data processing in the Internet of Things (IoT) environments, among which the IoT cloud infrastructure is one of the most mature solutions. Typically, modern IoT cloud infrastructures have different kinds of configuration options. The diversity of configurations leads to frequent software configuration errors. Generally, troubleshooting configuration errors relies on finding the mapping relationship between configuration options in the documents (e.g., official manuals) and their read sites in the source code. Most current works still manually extract configuration read sites. Automated methods are not always interchangeable and they incur considerable time overheads and low extraction rates. In this paper, we propose CRSExtractor, an automatic technique for extracting configuration read sites based on intra-procedural analysis. Using our technique, configuration option read sites can be automatically identified and built into maps with configuration options. Evaluations on several core software systems of IoT cloud platforms, such as Hadoop and Cassandra, show that our approach performs well, with an accuracy rate of over 90% and efficiency nearly 20 times faster than previous works.

3.
Opt Express ; 31(26): 44444-44454, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38178515

RESUMO

An innovative approach has been proposed for adaptive bias control in optical IQ modulators. In contrast to traditional approaches that utilize sine dither, this method employs a linear frequency modulated (LFM) signal as the dither, associated with the fractional Fourier Transform (FrFT) to extract the bias point drift. The LFM signal, after undergoing FrFT, transforms into a compressed signal (CS) with energy concentration in the fractional domain. Utilizing this signal for bias point monitoring, the proposed method demonstrates robust bias control even in the presence of substantial interferences, as substantiated by comprehensive simulations and experimental investigations. Remarkably, in a 20-Gbaud 16QAM signal transmission, the proposed approach achieves stable control of the bias point for over 4 hours, even in the presence of voltage fluctuations, while effectively reducing the dither amplitude by half. Furthermore, it maintains a low bit error rate (BER) below 10-5 even under intentional external interference.

4.
Ther Clin Risk Manag ; 17: 489-496, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34079270

RESUMO

BACKGROUND: To evaluate the anatomic and functional outcomes in eyes of patients with macular edema (ME) caused by central retinal vein occlusion (CRVO) who were lost to follow-up (LTFU) for more than 6 months following treatment with anti-vascular endothelial growth factor (VEGF) therapy and to determine the predictive factors of visual prognosis in these patients. METHODS: This study was conducted as a retrospective, case series investigation. Patients whose eyes were receiving intravitreal anti-VEGF treatment for CRVO-ME, with the next follow-up visit occurring more than 6 months following treatment were identified. Baseline disease characteristics (at the last visit before being LTFU), cause and duration of treatment interruption, and the resulting disease progression, complications, and outcomes were assessed. Baseline characteristics predictive of visual outcome were also analyzed. RESULTS: This study included a total of 17 eyes of 17 patients. The mean duration of being LTFU was 7.8 ± 2.1 months. On the return visit after being LTFU, 7 of 17 eyes (41.2%) developed neovascular complications. Despite treatment, 12 eyes (70.1%) lost ≥3 best-corrected visual acuity (BCVA) lines, with 2 eyes (11.8%) developing a final BCVA of hand motion or more severe. At the final visit, the mean logarithm of minimal angle of resolution (logMAR) BCVA deteriorated significantly compared to before being LTFU (P < 0.001). The increasing duration of being LTFU is associated with a deterioration of visual acuity prognosis. CONCLUSION: In CRVO-ME patients who are receiving anti-VEGF therapy, unintentional treatment interruptions can cause visually disastrous consequences, including irreversible blindness. Patients who were LTFU for a long period should be strongly warned about their poor visual prognosis.

5.
Retina ; 41(4): 834-843, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33755650

RESUMO

PURPOSE: This study aimed to investigate the effect of intravitreal conbercept (IVC) injections on the aqueous humor concentrations of angiogenic and inflammatory cytokines in patients with macular edema (ME) due to central retinal vein occlusion and to determine whether changes in cytokine levels after IVC are associated with the development of rebound ME. METHODS: Forty-nine patients with ME caused by central retinal vein occlusion were included in this retrospective study. Monthly doses of IVC were administered for three months, followed by a Pro Re Nata dosing regimen. Rebound ME was defined as ≥110% increase in the foveal thickness compared with the baseline. Whenever injections were administered, aqueous humor samples were obtained. Multiplex bead assay was used to measure seven angiogenic and inflammatory cytokines in aqueous humor samples. RESULTS: At baseline, patients with central retinal vein occlusion showed significantly higher aqueous humor concentrations of vascular endothelial growth factor, placental growth factor, monocyte chemoattractant protein-1, platelet-derived growth factor-AA, IL-6, IL-8, and IL-12. At 1-month and 2-month follow-up after IVC, significantly decreased concentrations of all cytokines were observed. During the 12-month follow-up period, 6 of the 49 eyes (12.2%) showed rebound ME after IVC. Patients with rebound ME showed significantly elevated levels of inflammatory but not angiogenic cytokines. CONCLUSION: Angiogenic and inflammatory cytokines were overexpressed in patients with ME caused by central retinal vein occlusion. Conbercept treatment influenced the concentrations of various inflammatory cytokines and reduced aqueous vascular endothelial growth factor and placental growth factor concentrations. Rebound ME may occur due to disruption of the balance between angiogenic and inflammatory cytokines and an accompanying excess of inflammatory cytokines but not angiogenic cytokines, after antivascular endothelial growth factor therapy.


Assuntos
Humor Aquoso/metabolismo , Citocinas/metabolismo , Edema Macular/metabolismo , Proteínas Recombinantes de Fusão/uso terapêutico , Oclusão da Veia Retiniana/tratamento farmacológico , Adulto , Idoso , Inibidores da Angiogênese/uso terapêutico , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Edema Macular/diagnóstico , Masculino , Pessoa de Meia-Idade , Recidiva , Oclusão da Veia Retiniana/metabolismo , Estudos Retrospectivos , Tomografia de Coerência Óptica , Acuidade Visual
6.
J Ocul Pharmacol Ther ; 37(1): 52-59, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33216685

RESUMO

Purpose: To analyze changes in the levels of angiogenic and inflammatory cytokines following the administration of intravitreal conbercept (IVC) or intravitreal ranibizumab (IVR) in patients with macular edema (ME) due to central retinal vein occlusion (CRVO). Methods: This retrospective study was conducted between June 2015 and January 2016 in The First Hospital of China Medical University. We administered 3 consecutive monthly doses of IVC (23 eyes) or IVR (19 eyes) in 42 eyes with CRVO-ME. At each injection, we collected aqueous humor samples and used multiplex bead assays to measure 7 angiogenic and inflammatory cytokines [vascular endothelial growth factor (VEGF), placental growth factor (PlGF), platelet-derived growth factor (PDGF)-AA, monocyte chemoattractant protein (MCP)-1, and interleukins (ILs)-6, 8, and 12]. Results: Visual acuity and ME improved significantly in both groups during the treatment period. Compared with the baseline, all the cytokine concentrations in the aqueous humor samples decreased significantly at 1 and 2 months after the initial dose of IVC or IVR. The improvement of visual acuity and ME and the changes of aqueous humor cytokine levels were similar in both groups. Concentrations of VEGF, PlGF, MCP-1, PDGF-AA, IL-6, IL-8, and IL-12 levels did not show significant intergroup differences after 1 month (P = 0.369, 0.312, 0.185, 0.353, 0.135, 0.487, and 0.337, respectively) and 2 months (P = 0.305, 0.376, 0.230, 0.519, 0.114, 0.960, and 0.830, respectively) of follow-up. Conclusion: IVC and IVR induced comparable improvements in clinical parameters, along with equivalent reductions in the concentrations of angiogenic and inflammatory cytokines in the aqueous humor.


Assuntos
Humor Aquoso/efeitos dos fármacos , Citocinas/antagonistas & inibidores , Edema Macular/tratamento farmacológico , Ranibizumab/farmacologia , Proteínas Recombinantes de Fusão/farmacologia , Oclusão da Veia Retiniana/tratamento farmacológico , Humor Aquoso/química , Citocinas/análise , Relação Dose-Resposta a Droga , Feminino , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Ranibizumab/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Estudos Retrospectivos
7.
World J Clin Cases ; 8(23): 6071-6079, 2020 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-33344607

RESUMO

BACKGROUND: Waldenström macroglobulinemia (WM) is a distinct clinicopathologic entity characterized by the infiltration of the bone marrow by clonal lymphoplasmacytic cells that produce monoclonal immunoglobulin M (IgM) in the blood, and patients may present with symptoms related to the infiltration of the hematopoietic tissues or the effects of monoclonal IgM in the blood. Funduscopic abnormalities were noted in some of the patients due to hyperviscosity or other retinal lesions. Optical coherence tomography angiography (OCTA) as a non-invasive imaging tool can give qualitative and quantitative information about the status of retinal and choroidal vessels, which might be useful for diagnosing patients with WM-associated retinopathy. CASE SUMMARY: The patient was a 67-year-old man who presented with sudden visual disturbance in both eyes. Ophthalmic tests showed that best corrected visual acuity (BCVA) for this patient was 20/100 in the right eye and 20/1000 in the left eye. Fundus examination, optical coherence tomography (OCT), and OCTA revealed substantial bilateral optic disc edema, dilated and tortuous retinal veins, and diffuse intraretinal blot hemorrhages and edema which were consistent with bilateral central retinal vein occlusion (CRVO). Meanwhile, remarkable bilateral serous macular detachments (SMD) were noticed on OCT. Systemic examinations showed that the patient had anemia and extremely high level of monoclonal IgM and infiltration of clonal lymphoplasmacytic cells in bone marrow. The diagnosis of WM with hyperviscosity and retinopathy was made based on the clinical manifestation and laboratory findings. He was subsequently treated with intravitreal ranibizumab injection, plasmapheresis, and bortezomib plus rituximab with dexamethasone. Six months after treatments, the central macular volume decreased by 16.1% in the right eye and 28.6% in the left eye on OCT, and the patient's BCVA was improved to 20/60 in the right eye and 20/400 in the left eye. Very good partial response was obtained after systemic treatment. CONCLUSION: WM may affect visual function and present as bilateral CRVO. OCTA can show characteristic changes in both retina and choroid vasculatures, which might be of great value for diagnosing or following patients with WM retinopathy. Intravitreal anti-vascular endothelial growth factor treatment combined with systemic therapy might be beneficial for WM patients with retinopathy (SMD and CRVO).

8.
Drug Des Devel Ther ; 14: 4205-4214, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116408

RESUMO

AIM: To examine the effects of platelet-activating factor (PAF) on the barrier functions of cultured retinal pigment epithelial (RPE) cells. METHODS: A human RPE cell line (ARPE-19) was cultured on microporous filter supports and treated with PAF and WEB 2086, a specific PAF-receptor (PAF-R) antagonist. The permeability of the RPE monolayer was measured using transepithelial electrical resistance (TER) and sodium fluorescein flux. The expression of the tight junction protein zonula occludens (ZO)-1 and the adherens junction protein N-cadherin was assessed using immunohistochemistry and Western blotting. We also measured the vascular endothelial growth factor (VEGF) concentrations in PAF-treated cultures and re-measured RPE monolayer permeability in the presence of VEGF-neutralizing antibodies. RESULTS: PAF significantly decreased the TER and enhanced the sodium fluorescein flux of the RPE monolayer and downregulated the expression of ZO-1 and N-cadherin. These effects were abolished by WEB 2086-mediated blockage of the PAF-R. PAF stimulation increased VEGF expression in RPE cells, and the antibody-mediated neutralization of VEGF caused a partial recovery of the barrier properties. CONCLUSION: The barrier functions of ARPE-19 cells were altered by PAF, and these effects were partly mediated by an upregulation of VEGF expression in these cells. Our results contribute to the growing body of evidence supporting the role of PAF in choroidal neovascularization. Our findings suggest that PAF is a novel target in the development of therapies for increased permeability of the RPE monolayer.


Assuntos
Fator de Ativação de Plaquetas/farmacologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Azepinas/farmacologia , Caderinas/efeitos dos fármacos , Linhagem Celular , Permeabilidade da Membrana Celular/efeitos dos fármacos , Impedância Elétrica , Humanos , Neovascularização Fisiológica/efeitos dos fármacos , Fator de Ativação de Plaquetas/antagonistas & inibidores , Inibidores da Agregação Plaquetária/farmacologia , Epitélio Pigmentado da Retina/citologia , Junções Íntimas/efeitos dos fármacos , Triazóis/farmacologia , Fator A de Crescimento do Endotélio Vascular/biossíntese , Proteína da Zônula de Oclusão-1/efeitos dos fármacos
9.
Sci Rep ; 10(1): 16959, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046787

RESUMO

This study aimed to evaluate the efficacy and safety of the intravitreal injection of conbercept in the treatment of macular neovascularization (MNV) secondary to high myopia and to observe the application of optical coherence tomography angiography (OCTA) in the treatment follow-up. We reviewed the medical records of 20 patients (21 eyes) with MNV secondary to high myopia who were enrolled in the Department of Ophthalmology of the First Hospital of China Medical University between May 2018 and January 2020. Each patient received one or more intravitreal injections of conbercept (0.5 mg/0.05 mL). The treatment was conducted according to a 1 + PRN (pro re nata) regimen. The changes of best corrected visual acuity (BCVA), central macular thickness (CMT), and selected MNV and flow areas measured by OCTA were observed over a 6-month follow-up period. The mean logarithm of the minimum angle of resolution (logMAR) BCVA was 1.03 ± 0.61 before treatment and improved to 0.83 ± 0.59 (P = 0.007), 0.78 ± 0.62 (P = 0.001), 0.81 ± 0.73 (P = 0.027), and 0.79 ± 0.72 (P = 0.023) at 1 month, 2 months, 3 months, and 6 months after treatment, respectively. The mean CMT was 358.16 ± 206.11 µm before treatment and decreased to 295.38 ± 178.70 µm (P = 0.003), 288.34 ± 165.60 µm (P = 0.004), 284.36 ± 163.07 µm (P = 0.005), and 283.00 ± 160.32 µm (P = 0.004) at 1 month, 2 months, 3 months, and 6 months after treatment, respectively. Nineteen eyes (90.5%) had stable or improved vision at 6 months of follow-up. One month after conbercept injection, in OCTA images, the small-diameter blood vessels of the MNV decreased, the intertwined small blood vessels decreased or even disappeared, and the main or larger-diameter blood vessels were still present. The mean selected MNV and blood flow areas were 0.62 ± 0.81 and 0.22 ± 0.27 mm2, respectively, before treatment and decreased to 0.23 ± 0.33 and 0.07 ± 0.08 mm2 (P = 0.04 for both), respectively, 1 month after treatment. No drug-related systemic or ocular adverse effects were observed. Our results suggest that conbercept can effectively and safely improve BCVA and reduce CMT in patients with myopic MVN (mMNV). OCTA can be used to observe MNV area, blood flow area, and MNV morphological changes after treatment with conbercept, thus providing a reference for treatment follow-up.


Assuntos
Neovascularização de Coroide/tratamento farmacológico , Miopia/complicações , Proteínas Recombinantes de Fusão/administração & dosagem , Idoso , Neovascularização de Coroide/etiologia , Neovascularização de Coroide/patologia , Neovascularização de Coroide/fisiopatologia , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade Visual
10.
J Ocul Pharmacol Ther ; 35(3): 161-167, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30668279

RESUMO

PURPOSE: We compared the efficacies of intravitreal ranibizumab (IVR) and intravitreal conbercept (IVC) as the adjuvant pretreatments for vitrectomy with silicone oil infusion for tractional retinal detachment (TRD) secondary to proliferative diabetic retinopathy. METHODS: This retrospective study comprised 74 patients (79 eyes) who underwent vitrectomy with silicone oil tamponade for diabetic TRD. They received IVC (37 eyes) or IVR (42 eyes) at standard doses 3-5 days preoperatively and were followed up for ∼6 months. Anatomic success rate, intra- and postoperative complications, and visual outcomes were compared between both groups. RESULTS: Initial (IVC vs. IVR: 97% vs. 98%) and final anatomic success rates (100% in each group) and mean visual acuity changes were not significantly different (P = 0.46). Intraoperative complications [iatrogenic retinal breaks (P = 0.58) and intraoperative bleeding (P = 0.66)], postoperative complications [fibrin formation (P = 0.51), postoperative preretinal bleeding (P = 0.88), progressing or persistent neovascular glaucoma (P = 0.63), progressive fibrovascular proliferation (P = 0.93), and recurrent retinal detachment (P = 0.93)], and surgical variables [surgical time (P = 0.53)] were similar between both groups. CONCLUSIONS: Conbercept and ranibizumab are equally effective surgical adjuvants for vitrectomy with silicone oil infusion in patients with diabetic TRD.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Ranibizumab/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Descolamento Retiniano/tratamento farmacológico , Óleos de Silicone/uso terapêutico , Inibidores da Angiogênese/administração & dosagem , Retinopatia Diabética/cirurgia , Humanos , Injeções Intravítreas , Pessoa de Meia-Idade , Ranibizumab/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Descolamento Retiniano/cirurgia , Estudos Retrospectivos , Óleos de Silicone/administração & dosagem , Vitrectomia
11.
Biochem Biophys Res Commun ; 508(1): 130-137, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30471863

RESUMO

Current clinical treatments for ocular neovascularization are characterized by high possibility of damaging healthy tissues and high recurrence rates. It is necessary to develop new treatment methods to control neovascularization with a stable and effective effect. Kringle1 domain of hepatocyte growth factor (HGFK1) has anti-angiogenesis activity. Here, we established oxygen-induced retinopathy (OIR) model to study if using adeno-associated virus (AAV) as a delivery system to overexpression HGFK1 in retinal cells could benefit retinal neovascularization. We show that, overexpressed exogenous gene was mainly expressed in the inner and outer nuclear layer of the retina. Compared with control mice, the mice pretreated with rAAV-HGFK1 at P3 showed relatively normal vascular branches examined by fluorescence fundus angiography. Subsequent H&E staining and immunohistochemical staining of CD31 of the eye tissue sections showed that the mice received rAAV-HGFK1 had a relatively normal distribution of vascular endothelial cells. Additionally, immunohistochemical staining indicated a lower expression of VEGF in the eye tissues of rAAV-HGFK1 treated OIR mice. Further in vitro studies showed that HGFK1 could inhibit the proliferation but promote the apoptosis of bovine retinal microvascular endothelial cells (BRECs) under the presence of VEGF. Moreover, HGFK1 could inhibit VEGF induced ERK activation but promote p38 activation in BRECs. Therefore, we propose that intravitreal injection of rAAV-HGFK1 might be used to improve the retinal neovascularization and HGFK1 may function through regulating VEGF signaling pathway to inhibit neovascularization.


Assuntos
Fator de Crescimento de Hepatócito/genética , Fator de Crescimento de Hepatócito/metabolismo , Neovascularização Retiniana/prevenção & controle , Animais , Apoptose , Bovinos , Proliferação de Células , Células Cultivadas , Dependovirus/genética , Modelos Animais de Doenças , Terapia Genética/métodos , Fator de Crescimento de Hepatócito/química , Humanos , Kringles/genética , Camundongos , Camundongos Endogâmicos C57BL , Oxigênio/administração & dosagem , Retina/metabolismo , Neovascularização Retiniana/genética , Neovascularização Retiniana/metabolismo , Vasos Retinianos/metabolismo , Vasos Retinianos/patologia , Transfecção , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/administração & dosagem
12.
Sensors (Basel) ; 18(3)2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29543773

RESUMO

With the development of the Internet-of-Things (IoT), wireless network security has more and more attention paid to it. The Sybil attack is one of the famous wireless attacks that can forge wireless devices to steal information from clients. These forged devices may constantly attack target access points to crush the wireless network. In this paper, we propose a novel Sybil attack detection based on Channel State Information (CSI). This detection algorithm can tell whether the static devices are Sybil attackers by combining a self-adaptive multiple signal classification algorithm with the Received Signal Strength Indicator (RSSI). Moreover, we develop a novel tracing scheme to cluster the channel characteristics of mobile devices and detect dynamic attackers that change their channel characteristics in an error area. Finally, we experiment on mobile and commercial WiFi devices. Our algorithm can effectively distinguish the Sybil devices. The experimental results show that our Sybil attack detection system achieves high accuracy for both static and dynamic scenarios. Therefore, combining the phase and similarity of channel features, the multi-dimensional analysis of CSI can effectively detect Sybil nodes and improve the security of wireless networks.

13.
Exp Ther Med ; 15(2): 1546-1551, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29434739

RESUMO

The aim of the present study was to evaluate the efficacy of combination treatment with intravitreal ranibizumab (IVR) injection and photodynamic therapy (PDT) for polypoidal choroidal vasculopathy (PCV). A total of 64 patients with PCV were included in the present study, which were divided into the IVR monotherapy group (Group A) and combination treatment groups (Groups B-D) with different treatment intervals. All subjects were followed-up at 1, 3, 6 and 12 months following treatment, and subjected to the detection of best-corrected visual acuity (BCVA) and central foveal thickness (CFT). Compared with the monotherapy group, more significant BCVA improvement was observed for the combination treatment groups, with the most evident effect exhibited in Group C. At the end of the follow-up period, visual acuity improvement rates were markedly elevated in the combination treatment groups, as compared with the monotherapy group. According to optical coherence tomography, the CFT for the combination treatment groups was thinner than the monotherapy group. Among the combination groups, CFT improvement for Group C was superior to other groups. Fundus angiography demonstrated that, compared with monotherapy, combination treatment may significantly promote the regression and prevent the recurrence of polyps and BVN. The most efficient effectiveness was observed for Group C. In addition, combination treatment may significantly reduce the IVR injection numbers required to treat PCV. Patients receiving combination treatment with IVR injection and PDT have greater vision improvements, reduced macular degeneration and decreased injection numbers. Combination therapy may therefore, represent an effective and safe therapeutic strategy for PCV clinical treatment.

14.
Int J Ophthalmol ; 10(4): 535-540, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28503424

RESUMO

AIM: o identify the effects of interleukin (IL)-13 on retinal pigment epithelial (RPE) cells and the IL-13 level in aqueous humor of age-related macular degeneration (AMD) patients. METHODS: IL-13 levels in aqueous humor specimens from AMD patients were detected with enzyme-linked immunosorbent assay (ELISA). ARPE-19 cells were treated with 10 ng/mL IL-13 for 12, 24, and 48h. The cell proliferaton was evaluated by the MTS method. The mRNA and protein levels of α-SMA and ZO-1 were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot respectively. The expression of tumor necrosis factor-α (TNF-α), transforming growth factor-ß (TGF-ß) and vascular endothelial growth factor (VEGF) were assessed by ELISA. RESULTS: IL-13 levels in the aqueous humor of patients with AMD were significantly higher than those in the control (167.33±17.64 vs 27.12±5.65 pg/mL; P<0.01). In vitro, IL-13 of high concentrations (10, 15, and 20 ng/mL) inhibited ARPE-19 cell proliferation. α-SMA mRNA in ARPE-19 cell were increased (1.017±0.112 vs 1.476±0.168; P<0.001) and ZO-1 decreased (1.051±0.136 vs 0.702±0.069; P<0.001) after treated with 10 ng/mL IL-13 for 48h. The protein expression of α-SMA and ZO-1 also showed the same tendency (α-SMA: P=0.038; ZO-1: P=0.008). IL-13 significantly reduced the level of TNF-α (44.70±1.67 vs 31.79±3.53 pg/mL; P=0.005) at 48h, but the level of TGF-ß2 was significantly increased from 34.44±2.92 to 57.61±6.31 pg/mL at 24h (P=0.004) and from 61.26±1.11 to 86.91±3.59 pg/mL at 48h (P<0.001). While expressions of VEGF didn't change after IL-13 treatment. CONCLUSION: IL-13 in vitro inhibit ARPE-19 cell proliferation and expression in the aqueous may be associated with AMD.

15.
PLoS One ; 11(1): e0146808, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26760305

RESUMO

Choroidal neovascularization (CNV) is an important pathologic component of neovascular age-related macular degeneration (AMD), and CNV lesions later develop into fibrous scars, which contribute to the loss of central vision. Nowadays, the precise molecular and cellular mechanisms underlying CNV and subretinal fibrosis have yet to be fully elucidated. Cyclooxygenase-2 (COX-2) has previously been implicated in angiogenesis and fibrosis. However, the role of COX-2 in the pathogenesis of CNV and subretinal fibrosis is poorly understood. The present study reveals several important findings concerning the relationship of COX-2 signaling with CNV and subretinal fibrosis. Experimental CNV lesions were attenuated by the administration of NS-398, a COX-2-selective antagonist. NS-398-induced CNV suppression was found to be mediated by the attenuation of macrophage infiltration and down-regulation of VEGF in the retinal pigment epithelium-choroid complex. Additionally, NS-398 attenuated subretinal fibrosis, in an experimental model of subretinal scarring observed in neovascular AMD, by down-regulation of TGF-ß2 in the retinal pigment epithelium-choroid complex. Moreover, we cultured mouse RPE cells and found that NS-398 decreased the secretion of VEGF and TGF-ß2 in mouse RPE cells. The results of the present study provide new findings regarding the molecular basis of CNV and subretinal fibrosis, and provide a proof-of-concept approach for the efficacy of COX-2 inhibition in treating subretinal fibrosis.


Assuntos
Neovascularização de Coroide/tratamento farmacológico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Nitrobenzenos/uso terapêutico , Retina/patologia , Sulfonamidas/uso terapêutico , Animais , Corioide/efeitos dos fármacos , Corioide/metabolismo , Corioide/patologia , Neovascularização de Coroide/patologia , Inibidores de Ciclo-Oxigenase/farmacologia , Modelos Animais de Doenças , Fibrose , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Camundongos Endogâmicos C57BL , Nitrobenzenos/farmacologia , Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Sulfonamidas/farmacologia , Fator de Crescimento Transformador beta2/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
16.
Int J Ophthalmol ; 7(2): 194-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24790857

RESUMO

AIM: To determine the involvement of the interleukin (IL)-6 with the development of experimental subretinal fibrosis in a mouse model. METHODS: Subretinal fibrosis was induced by subretinal injection of macrophage-rich peritoneal exudate cells and the local expression of IL-6 was assessed by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) at various time points. In addition, we investigated the effect of IL-6 receptor (IL-6R) monoclonal antibody (MR16-1) on subretinal fibrosis development. RESULTS: IL-6 mRNA level was significantly elevated at 1d after subretinal fibrosis induction and increased further to about 12-fold at 2d, reaching the peak. The result of ELISA showed that IL-6 protein was not detected in naive mice. At 2d after subretinal fibrosis induction, IL-6 protein level was upregulated to 67.33±14.96 pg/mg in subretinal fibrosis mice. MR16-1 treatment resulted in a reduced subretinal fibrosis area by 48% compared to animals from control group at 7d. CONCLUSION: Our results indicated that IL-6 signaling may contribute to the pathogenesis of subretinal fibrogenesis and IL-6R inhibition may provide an effective, novel treatment of advanced and late-stage neovascular age-related macular degeneration.

17.
Int J Ophthalmol ; 6(2): 169-73, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23638418

RESUMO

AIM: To compare the clinical efficacy of intravitreal injections of bevacizumab and ranibizumab for treating Chinese patients with neovascular age-related macular degeneration (AMD). METHODS: Among 60 Chinese patients with exudative AMD (60 eyes), 28 received intravitreal bevacizumab injections (1.25mg) and 32 received intravitreal ranibizumab injections (0.5mg), once a month for 3 months and were followed for a total of 6 months. Monthly optical coherence tomography (OCT) was used to determine whether the patients received additional treatments during the follow-up. We compared the baseline and 6-month follow-up values of mean best-corrected visual acuity (BCVA) and central retinal thickness (CRT) in both groups of patients. We also compared the occurrence of adverse events. RESULTS: At the 6-month follow-up, the mean BCVA (logMAR) of the bevacizumab and ranibizumab treatment groups improved from the baseline measurements of 0.72±0.23 and 0.73±0.22 to 0.47±0.14 and 0.45±0.20, respectively (P<0.05 for both groups). However, the change was not significantly different between the two groups. As evaluated by OCT, CRT decreased from 366.71±34.72µm and 352±36.9µm at baseline to 250.86±41.51µm and 243.22±41.38µm in the bevacizumab and ranibizumab groups, respectively (P<0.05 for both groups). However, the change was not significantly different between the two groups. There were no severe local adverse reactions or systemic adverse events. CONCLUSION: Intravitreal bevacizumab and ranibizumab have equivalent effects on BCVA and CRT and appeare safe over the short-term.

18.
Int J Ophthalmol ; 5(3): 307-11, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22773978

RESUMO

AIM: To determine the involvement of the transforming growth factor (TGF)-ß with the development of experimental subretinal fibrosis in a mouse model. METHODS: Subretinal fibrosis was induced by subretinal injection of macrophage-rich peritoneal exudate cells (PECs) and the local expression of TGF-ß isoforms was assessed by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) at various time points. In addition, we investigated the effect of TFG-ß-neutralizing antibodies (TGF-ß NAb) on subretinal fibrosis development. RESULTS: TGF-ß1 and TGF-ß2 mRNA level was significantly elevated at day 2 after subretinal fibrosis induction and increased further to 5 and 6.5-fold respectively at day 5, reaching the peak. TGF-ß3 mRNA was not detected in the present study. The result of ELSIA showed that active TGF-ß1 and TGF-ß2 levels were upregulated to 10-fold approximately, while total TGF-ß1 and TGF-ß2 levels were even upregulated more than 10-fold and more than 20-fold respectively in subretinal fibrosis mice in comparison with naïve mice at day 5. TGF-ß NAb resulted in a reduced subretinal fibrosis areas by 65% compared to animals from control group at day 7. CONCLUSION: Our results indicate that TGF-ß signaling may contribute to the pathogenesis of subretinal fibrogenesis and TGF-ß inhibition may provide an effective, novel treatment of advanced and late-stage neovascular age-related macular degeneration.

19.
Retina ; 32(6): 1106-13, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22481479

RESUMO

PURPOSE: To evaluate the efficacy and safety of intravitreal bevacizumab as primary treatment of choroidal neovascularization secondary to punctate inner choroidopathy. METHODS: Twelve eyes of 12 patients with subfoveal or juxtafoveal choroidal neovascularization secondary to punctate inner choroidopathy received intravitreal bevacizumab injection (1.25 mg) in this prospective case series. Injection was repeated if persistent or recurrent activity of choroidal neovascularization was indicated by optical coherence tomography or fundus fluorescein angiography at 1-month intervals. Visual, clinical, angiographic, and anatomical changes were observed over a 12-month follow-up period. RESULTS: After 12 months of follow-up, mean logarithm of the minimum angle of resolution best-corrected visual acuity improved from 0.49 (20/62 in Snellen equivalent) at baseline to 0.23 (20/34 in Snellen equivalent; P < 0.001). Mean central retinal thickness determined by optical coherence tomography decreased from 333 µm to 241 µm (P < 0.001). All eyes (100%) had stable or improved vision, and 9 eyes (75%) showed an improvement of ≥ 2 lines. All lesions converted to the cicatricial phase after 12 months of follow-up. No drug-related systemic or ocular side effects were observed. CONCLUSION: Intravitreal bevacizumab is well tolerated and improves best-corrected visual acuity in choroidal neovascularization secondary to punctate inner choroidopathy over a 12-month period.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Neovascularização de Coroide/tratamento farmacológico , Adulto , Bevacizumab , Doenças da Coroide/complicações , Neovascularização de Coroide/etiologia , Feminino , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Acuidade Visual , Adulto Jovem
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