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1.
Medicine (Baltimore) ; 99(7): e19102, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32049817

RESUMO

BACKGROUND: Traditional Chinese medicine (TCM) has been used to treat diabetic complications including diabetic retinopathy for many years. OBJECTIVES: This review was performed to systematically assess the efficacy and safety of TCM for treating non- proliferative diabetic retinopathy (NPDR). METHODS: Retrieval from 7 electronic databases was conducted to determine eligible trials published until March 1, 2018. Randomized controlled trials of NPDR that comparing compound Chinese medicine containing the therapeutic method of activating blood and remove stasis versus controls were included for analysis. Primary outcomes were progression of retinopathy. Secondary outcomes included visual acuity, mean defect of visual field, micro-aneurysms, hemorrhage areas, exudates, capillary nonperfusion areas, hemorheological indicators, oscillatory potentials (Ops), glycated haemoglobin (HbA1c), and adverse events. Data extraction and quality assessment were performed. Results expressing as risk ratios (RRs) or mean differences (MD) were analyzed with a fixed- or random- effect model. I statistics were used to assess heterogeneity. RESULTS: A total of 33 trials and 3373 participants were included. Findings revealed that no included studies reported the progression of retinopathy. Compared with conventional medicine, TCM was significantly better at improving visual acuity (MD, -0.10; 95% confidence interval [CI] -0.16 to -0.05) and Ops (MD, -4.68, 95% CI -8.51 to -0.85), and reducing the mean defect of visual field (MD, -1.43; 95%CI, -2.17 to -0.68), micro-aneurysms (MD, -4.51; 95% CI, -6.23 to -2.79), hemorrhage areas (MD, -0.62; 95% CI, -1.06 to -0.19), plasma viscosity (MD, -0.10; 95% CI, -0.20 to 0.00), and HbA1c (MD, -0.22; 95% CI, -0.42 to -0.03). Compared with placebo, TCM was also associated with a decline in the number of microaneurysms (MD, -4.35; 95% CI, -6.25 to -2.45), exudates (MD, -0.17; 95% CI -0.31 to -0.03), capillary nonperfusion areas (MD, -0.18; 95% CI, -0.31 to -0.04), and HbA1c (MD, -0.88; 95% CI, -1.44 to -0.32). Compared with blank groups, TCM was superior at decreasing the mean defect of visual field (MD, -0.87; 95% CI -0.95 to -0.79) and the numbers of micro-aneurysms (MD, -3.35; 95% CI, -4.73 to -1.97). Adverse events were also assessed. CONCLUSION: Activating blood compound Chinese herbal medicine could help to improve visual acuity, micro-aneurysms and HbA1c. Further trials are needed to provide more reliable evidence.


Assuntos
Retinopatia Diabética/tratamento farmacológico , Medicina Tradicional Chinesa/métodos , Adulto , Idoso , Retinopatia Diabética/sangue , Progressão da Doença , Feminino , Humanos , Masculino , Medicina Tradicional Chinesa/efeitos adversos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Acuidade Visual/efeitos dos fármacos
2.
Life Sci ; 245: 117350, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31982401

RESUMO

Resveratrol is an important phenolic phytochemical from the therapeutic perspective. It has therapeutic impacts over wide range of diseases, especially the ones related to oxidative stress. Resveratrol, being primarily a potent anti-oxidant phytochemical, has significant impact against major diseases as inflammatory disorders, diabetes, and cancer. In the current review article, we intend to highlight the molecular aspects of the mechanism of action of resveratrol against major diabetic implications, namely, retinopathy and neuropathy. Both these diabetic implications are among the first fallouts of chronic hyperglycaemia. Resveratrol, via multiple molecular pathways, tend to attenuate and reverse these deformity and other disease-causing implications.


Assuntos
Antioxidantes/uso terapêutico , Neuropatias Diabéticas/tratamento farmacológico , Retinopatia Diabética/tratamento farmacológico , Resveratrol/uso terapêutico , Animais , Antioxidantes/farmacologia , Humanos , Resveratrol/farmacologia
3.
Klin Monbl Augenheilkd ; 237(1): 79-84, 2020 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-30736075

RESUMO

PURPOSE: Diabetic retinopathy is one of the worst complications of diabetes and can threaten sight. The aim of our study is to compare the clinical outcomes and ultrastructural changes in diabetic retinopathy patients after intravitreal admission of either ranibizumab (Lucentis) or aflibercept (Eylea). METHODS: In our prospective study, 27 patients with PDR were enrolled. They were divided into two groups - 14 PDR patients treated with ranibizumab and 13 PDR patients treated with aflibercept. In both groups, a complete ophthalmological examination was performed, including OCT. In 12 patients (6 from each group), pars plana vitrectomy was performed with excision of epiretinal membranes. Transmission and scanning electron microscopy of the membranes was performed. RESULTS: Clinical findings - in both groups there was a decrease in the neovascular proliferation and macular oedema. CRT was reduced with approximately 100 - 120мk. In the Eylea group, there was general shrinking of neovascular proliferation with lower risk of bleeding. The ultrastructural analysis showed more significant reduction in endothelial fenestration after Eylea application, with clustering of platelets and erythrocytes in the capillary lumen. Increased numbers of macrophages were found in the membranes of both groups. CONCLUSION: Our results show that aflibercept is very effective in treating PDR. It causes more significant reduction of endothelial fenestration and more evident thrombotic microangiopathy than other anti-VEGF drugs, and thus diminishes macular oedema and prevents neovascular tissue from bleeding. Eylea inhibits both VEGF and placental growth factor and thus modifies the whole pathophysiology of DR. It is therefore more effective than other treatment medications.


Assuntos
Inibidores da Angiogênese , Retinopatia Diabética , Ranibizumab , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão , Inibidores da Angiogênese/administração & dosagem , Retinopatia Diabética/tratamento farmacológico , Humanos , Injeções Intravítreas , Estudos Prospectivos , Ranibizumab/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Fator A de Crescimento do Endotélio Vascular
4.
Eur J Ophthalmol ; 30(1): 34-39, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30539668

RESUMO

PURPOSE: To compare the outcome of the sequence in the two treatments (intravitreal ranibizumab and panretinal photocoagulation) in high-risk proliferative diabetic retinopathy. METHODS: This retrospective study included 35 patients with newly diagnosed high-risk proliferative diabetic retinopathy in 43 eyes; 18 (22 eyes) received intravitreal ranibizumab before panretinal photocoagulation (intravitreal ranibizumab+ group), while the other 17 (21 eyes) received panretinal photocoagulation before intravitreal ranibizumab (panretinal photocoagulation+ group). Each subject received three intravitreal ranibizumabs that were interleaved with three panretinal photocoagulations. The first treatment (either intravitreal ranibizumab or panretinal photocoagulation) was done 1 week before the second one. The interval between intravitreal ranibizumabs was 4 weeks, panretinal photocoagulation was 2 weeks. The power and pulse duration were determined based upon the status of each retinal spot before each panretinal photocoagulation. The retinal non-perfusion region was measured with fundus fluorescein angiography before and 1 month after the final treatment. The central macular thickness was measured with optical coherence tomography within 1 week before the first treatment, before each panretinal photocoagulation, and 1 month after the final intravitreal ranibizumab. RESULTS: The panretinal photocoagulation energy required for effective treatment was lower in intravitreal ranibizumab+ group in the first and second sessions and in total energy (p < 0.05). Central macular thickness reduction before the second panretinal photocoagulation session was significant in the intravitreal ranibizumab+ group (p < 0.05). CONCLUSION: The sequence used in intravitreal ranibizumab+ group showed clear advantages over that in panretinal photocoagulation+ group in the treatment of proliferative diabetic retinopathy, not only in the use of lower energy for panretinal photocoagulation but also in the more rapid regression of neovascularization and less need of additional treatment.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Retinopatia Diabética/terapia , Fotocoagulação a Laser , Ranibizumab/uso terapêutico , Adulto , Protocolos Clínicos , Terapia Combinada , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/fisiopatologia , Retinopatia Diabética/cirurgia , Feminino , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Retina/fisiopatologia , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual
5.
Eur J Ophthalmol ; 30(1): 72-80, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30764665

RESUMO

PURPOSE: To determine whether anemia and other demographic or laboratory "risk factors" impact anti-vascular endothelial growth factor treatment in diabetic macular edema patients. METHODS: This is a retrospective, time-varying cohort study using a medical claims database to identify new diabetic macular edema patients who had received at least one intravitreal injection of anti-vascular endothelial growth factor. Exclusion occurred for having <2 years in the plan prior to diabetic macular edema diagnosis, any history of proliferative retinopathy or any treatment that is used for diabetic macular edema. Covariates of interest were demographic characteristics, laboratory values, and clinical factors such as previous anti-vascular endothelial growth factor used, number of involved eyes, year of treatment, and time since last injection. Those variables that changed with time were assessed and updated at each visit. The main outcome measure was the odds of receiving treatment at any visit. RESULTS: In total, 189 new diabetic macular edema patients with follow-up were analyzed, covering 729 visits with 543 (74.5%) receiving treatment. Univariate analysis showed that male gender (odds ratio: 0.54, 95% confidence interval: 0.32-0.91, p = 0.03), every week since last injection (odds ratio: 0.94, 95% confidence interval: 0.91-0.97, p = 0.001), and having two eyes affected (odds ratio: 2.09, 95% confidence interval: 1.10-3.97, p = 0.02) were associated with getting an injection. After multivariate analysis, only time since previous injection with every week that passed reduced the odds on having an injection at the next visit (odds ratio: 0.95, 95% confidence interval: 0.92-0.97, p < 0.001). Anemia was not associated with receiving an injection (odds ratio: 1.05, 95% confidence interval: 0.61-1.80, p = 0.86). CONCLUSION: This study used time-varying methodology to better identify which patients will likely need an injection at any one visit. While anemia was not found to impact injections, our results can aid future endeavors that may incorporate clinical visit information in developing a full prediction model to help make diabetic macular edema care more efficient.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Edema Macular/tratamento farmacológico , Idoso , Anemia/complicações , Bevacizumab/uso terapêutico , Estudos de Coortes , Retinopatia Diabética/diagnóstico , Feminino , Humanos , Injeções Intravítreas , Edema Macular/diagnóstico , Masculino , Pessoa de Meia-Idade , Ranibizumab/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia
6.
J Ethnopharmacol ; 247: 112275, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31589966

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic retinopathy (DR) is a terrible microvascular disorder causing blindness. Retinal inflammation is the early stage in DR, which is believed to play a crucial role in the development of it. Shengpuhuang-tang (ST), a traditional herbal formula, which has effective treatment of fundus bleeding disorder. ST exerts protective effects against DR in rats, but its underlying mechanism of this efficacy remains unknown. Thus, the objective of this study is to examine the mechanism and the efficacy of ST on retinal inflammation in streptozotocin-induced diabetic rats. MATERIALS AND METHODS: The administration of ST was initiated at 4 weeks after diabetes induction and continued for 12 weeks. Retinal vessel permeability was evaluated by using FITC-dextran and Evans blue. Retinal leukostasis was evaluated with FITC-coupled concanavalin A lectin (ConA). Moreover, western blotting was performed to detect TNF-α, ICAM-1 and the relative expression levels of IκBα, IKKß, and p65 in vivo. RESULTS: The results showed that the retinal inflammation in streptozotocin-induced diabetic rats was significantly decreased by ST. ST could decreased the expression levels of TNF-α, ICAM-1 and inhibited the expression of p-IKKß, p-p65 and IκBα. It could also inhibited the nuclear transfer of p65. CONCLUSIONS: In conclusion, these data suggested that ST may have potential treatment strategies against early stage of diabetic retinopathy through NF-κB pathway.


Assuntos
Diabetes Mellitus Experimental/complicações , Retinopatia Diabética/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Leucostasia/tratamento farmacológico , Vasos Retinianos/efeitos dos fármacos , Administração Oral , Animais , Capilares/efeitos dos fármacos , Capilares/metabolismo , Capilares/patologia , Permeabilidade Capilar/efeitos dos fármacos , Diabetes Mellitus Experimental/induzido quimicamente , Retinopatia Diabética/etiologia , Retinopatia Diabética/patologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Leucostasia/etiologia , Masculino , NF-kappa B/imunologia , NF-kappa B/metabolismo , Ratos , Vasos Retinianos/metabolismo , Vasos Retinianos/patologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Estreptozocina/toxicidade
7.
Adv Exp Med Biol ; 1185: 469-473, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31884656

RESUMO

The concept that Müller glia (MG) are major retinal supporting cells for neuroprotection under various stresses is well established. However, the detailed molecular and cellular mechanisms of MG-mediated neuroprotection remain elusive. Particularly, the role and mechanism of MG in neuroprotection under diabetic and hypoxic stresses are largely unknown. In this article, we will discuss the role and mechanisms of a major growth factor, vascular endothelial growth factor (VEGF), in mediating MG viability and its potential impact on neuronal integrity in diabetes and hypoxia, demonstrate results on alternative mechanisms to VEGF signaling for MG and neural protection, and highlight the relevance of our work to the treatment of neovascular age-related macular degeneration, diabetic retinopathy, wet age-related macular degeneration, and other hypoxic retinal vascular diseases.


Assuntos
Retinopatia Diabética/tratamento farmacológico , Neuroglia/efeitos dos fármacos , Neuroproteção , Fator A de Crescimento do Endotélio Vascular/fisiologia , Degeneração Macular Exsudativa/tratamento farmacológico , Diabetes Mellitus , Humanos , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
8.
Medicine (Baltimore) ; 98(51): e18333, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31860985

RESUMO

To determine characteristics of diabetic macular edema patients with serous retinal detachment (SRD).We classified naïve diabetic macular edema (DME) patients with or without SRD, and compared their baseline characteristics; intravitreal bevacizumab (IVB) responsiveness; aqueous concentrations of IL (interleukin)-1ß, -2, -8, -10, -17, placental growth factor (PlGF), and vascular endothelial growth factor (VEGF). In addition, factors associated with the existence of SRD were identified.Of the 64 DME patients, 14 had SRD. The average levels of aqueous VEGF and PlGF were significantly higher in the SRD group than in the control group (P = .022 and P = .041, respectively). The best-corrected visual acuity (BCVA) and central subfield thickness (CST) did not differ significantly between the 2 groups at baseline or after 3 consecutive monthly IVBs. In multivariate logistic regression analysis, the level of aqueous VEGF was the only factor associated with the existence of SRD (odds ratio: 1.03; P = .038).Rather than aqueous inflammatory cytokines, levels of aqueous VEGFs were associated with the occurrence of SRD in DME patients. In terms of prognosis, the existence of SRD was not related with BCVA or CST changes.


Assuntos
Humor Aquoso/metabolismo , Bevacizumab/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Edema Macular/tratamento farmacológico , Descolamento Retiniano/tratamento farmacológico , Inibidores da Angiogênese/uso terapêutico , Estudos de Casos e Controles , Retinopatia Diabética/metabolismo , Feminino , Humanos , Interleucina-1beta/metabolismo , Injeções Intravítreas , Edema Macular/metabolismo , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Placentário/metabolismo , Prognóstico , Retina/patologia , Descolamento Retiniano/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Acuidade Visual/efeitos dos fármacos
9.
Ophthalmic Surg Lasers Imaging Retina ; 50(11): 684-690, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31755967

RESUMO

BACKGROUND AND OBJECTIVE: To report the correlation of central macular thickness (CMT) and best-corrected visual acuity (BCVA) after 1-year treatment by two doses (2.5 mg or 1.25 mg) of intravitreal ziv-aflibercept (IVZ) versus bevacizumab (IVB) in eyes with diabetic macular edema (DME). PATIENTS AND METHODS: In this study, the correlation of CMT and BCVA changes of the eyes enrolled in a previous clinical trial of 123 eyes were re-evaluated. The correlation of BCVA and CMT changes at each visit was evaluated in the three study arms individually. Then, the eyes in each of the arms were classified at each follow-up visit into three subgroups based on their CMT changes related to the baseline CMT: CMT decrease of 30% or more of baseline CMT, between 10% to 29% of baseline CMT, and less than 9% of baseline CMT or CMT increase. RESULTS: BCVA and CMT changes were correlated significantly (P < .05) in all and in half of the follow-up visits, respectively, in the eyes treated by IVZ 1.25 mg and IVB (r = 0.554 and r = 0.617 at 1 year, respectively). Nevertheless, such a significant correlation was not detected in the eyes treated by IVZ 2.5 mg in any of the follow-up visits (r = 0.202 at 1 year; P = .259). In the IVZ 2.5 mg group, BCVA improvement was observed in all subgroups with each level of CMT reductions. CONCLUSION: Ziv-aflibercept 2.5 mg might have a beneficial effect on DME beyond thickness reduction. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:684-690.].


Assuntos
Inibidores da Angiogênese/administração & dosagem , Bevacizumab/administração & dosagem , Retinopatia Diabética/complicações , Macula Lutea/patologia , Edema Macular/tratamento farmacológico , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Acuidade Visual/fisiologia , Adulto , Idoso , Retinopatia Diabética/tratamento farmacológico , Feminino , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Edema Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tomografia de Coerência Óptica
10.
Ophthalmic Surg Lasers Imaging Retina ; 50(11): e266-e273, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31755977

RESUMO

BACKGROUND AND OBJECTIVE: To evaluate the vitreomacular interface and its relation to treatment burden for diabetic macular edema (DME) in patients without overt vitreomacular traction (VMT). PATIENTS AND METHODS: A retrospective cohort study of 494 eyes from 274 patients who had macular spectral-domain optical coherence tomography (SD-OCT) and did not have proliferative diabetic retinopathy, DME, or VMT at the initial visit. Posterior vitreous detachment (PVD) was categorized at the initial visit into five stages (0-4) using SD-OCT parameters alone. RESULTS: Two of 34 eyes (6.9%) presenting with a complete PVD required DME treatment during follow-up, whereas 144 of 460 eyes (31.3%) without a complete PVD at baseline required treatment (P = .001, Chi-squared). After adjusting for age, ethnicity, gender, and HbA1c, complete PVD at baseline was associated with a significant reduction in risk of DME therapy (hazard ratio: 0.18; 95% confidence interval, 0.05-0.73; P = .02). CONCLUSION: Complete PVD is independently associated with a reduced need for DME treatment. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e266-e273.].


Assuntos
Inibidores da Angiogênese/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Edema Macular/tratamento farmacológico , Descolamento do Vítreo/patologia , Idoso , Idoso de 80 Anos ou mais , Humanos , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos
11.
Ophthalmic Surg Lasers Imaging Retina ; 50(11): e300-e310, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31755982

RESUMO

BACKGROUND AND OBJECTIVE: Diabetic macular edema (DME) is a leading cause of vision loss worldwide. The object of this study is to compare global differences of baseline characteristics of patients undergoing initiation of anti-vascular endothelial growth factor (VEGF) therapy for DME. PATIENTS AND METHODS: This multicenter, cross-sectional study included diabetic patients with foveal-involving retinal edema secondary to DME as documented by fundus exam and optical coherence tomography who were undergoing initiation of intravitreal anti-VEGF drugs. Variables were collected to find possible risk factors and to create an epidemiological profile of DME patients undergoing initiation of anti-VEGF agents. RESULTS: Nine hundred two patients were selected. Mean age was 62.4 (±11) years, 49.7% were Caucasians, 57.6% were male, and 96% had type two diabetes with an average disease duration of 181.7 months ± 113 months. Of the patients included, 74.7% suffered from hypertension, 26.6% from cardiovascular disease, 12.1% from cerebrovascular disease, 12.8% from peripheral vascular disease, and 12.8% from renal insufficiency. Best-corrected visual acuity (BCVA) was 65 (±20) Early Treatment Diabetic Retinopathy Study letters, central subfield thickness was 364 (±162) µm, cube volume 11.1 ± 3.1 mm3, cube average thickness 328.8 µm ± 61 µm, and 63.9% had nonproliferative diabetic retinopathy. Comparison between U.S. versus international patients, and patients with BCVA 70 letters or less versus more than 70 letters were performed, significant differences were acknowledged, and risk factors were recognized. CONCLUSION: There were key differences in the epidemiologic profile between patients presenting with DME in the U.S. and internationally. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e300-e310.].


Assuntos
Inibidores da Angiogênese/uso terapêutico , Retinopatia Diabética , Edema Macular , Ranibizumab/uso terapêutico , Idoso , Estudos Transversais , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/etiologia , Retinopatia Diabética/patologia , Retinopatia Diabética/fisiopatologia , Feminino , Humanos , Injeções Intravítreas , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Edema Macular/patologia , Edema Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Retina/patologia , Fatores de Risco , Acuidade Visual/fisiologia
12.
Int J Mol Sci ; 20(19)2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31590397

RESUMO

(1) Aims: The present study aimed to observe the effects of Ginsenoside Rb1 on high glucose-induced endothelial damage in rat retinal capillary endothelial cells (RCECs) and to investigate the underlying mechanism. (2) Methods: Cultured RCECs were treated with normal glucose (5.5 mM), high glucose (30 mM glucose), or high glucose plus Rb1 (20 µM). Cell viability, lactate dehydrogenase (LDH) levels, the mitochondrial DNA copy number, and the intracellular ROS content were measured to evaluate the cytotoxicity. Superoxide dismutase (SOD), catalase (CAT), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), poly(ADP-ribose) polymerase (PARP), and sirtuin (SIRT) activity was studied in cell extracts. Nicotinamide adenine dinucleotide (NAD+)/NADH, NADPH/NADP+, and glutathione (GSH)/GSSG levels were measured to evaluate the redox state. The expression of nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1), SIRT1, and SIRT3 was also evaluated after Rb1 treatment. (3) Results: Treatment with Rb1 significantly increased the cell viability and mtDNA copy number, and inhibited ROS generation. Rb1 treatment increased the activity of SOD and CAT and reduced the activity of NOX and PARP. Moreover, Rb1 enhanced both SIRT activity and SIRT1/SIRT3 expression. Additionally, Rb1 was able to re-establish the cellular redox balance in RCECs. However, Rb1 showed no effect on NMNAT1 expression in RCECs exposed to high glucose. (4) Conclusion: Under high glucose conditions, decreases in the reducing power may be linked to DNA oxidative damage and apoptosis via activation of the NMNAT-NAD-PARP-SIRT axis. Rb1 provides an advantage during high glucose-induced cell damage by targeting the NAD-PARP-SIRT signaling pathway and modulating the redox state in RCECs.


Assuntos
Antioxidantes/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Ginsenosídeos/uso terapêutico , Estresse Oxidativo , Vasos Retinianos/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Ginsenosídeos/farmacologia , Glucose/toxicidade , Masculino , NAD/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Ratos , Ratos Sprague-Dawley , Vasos Retinianos/citologia , Vasos Retinianos/metabolismo , Transdução de Sinais , Sirtuínas/metabolismo
13.
Vestn Oftalmol ; 135(4): 121-127, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31573567

RESUMO

Retinal damage in diabetes is known to manifest in two main ways: diabetic retinopathy and diabetic macular edema. The most effective anti-inflammatory drugs today are glucocorticoids, a classic representative of which is dexamethasone. Two things that should be considered by ophthalmologists in the therapy of macular edema are the switching point to dexamethasone implant when the effectiveness of anti-vasoproliferative drugs is unsatisfactory, and the identification of the main predictors of diabetic macular edema that make glucocorticoids the drugs of first choice. The data from real clinical practice was used to develop the indications for intravitreal administration of a glucocorticoid as the therapy of first choice for diabetic macular edema. Glucocorticoids are prescribed to patients diagnosed with diabetic macular edema who has a history of acute cerebrovascular events, myocardial infarction or other cardiovascular and cerebrovascular diseases, as well as patients with a very high risk of a vascular catastrophe. Intravitreal glucocorticoids can be prescribed to patients who cannot follow the schedule of frequent visits and/or are not able to visit the hospital during the first 6 months after the administration of the drug. Considering the local character of its ophthalmic action, the method can be recommended for treating patients with pseudophakic eyes, persistent diabetic macular edema, or patients who underwent vitrectomy.


Assuntos
Dexametasona/uso terapêutico , Retinopatia Diabética , Edema Macular , Retinopatia Diabética/tratamento farmacológico , Implantes de Medicamento , Humanos , Injeções Intravítreas , Edema Macular/tratamento farmacológico , Acuidade Visual
14.
Medicine (Baltimore) ; 98(42): e17496, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626104

RESUMO

BACKGROUND: Diabetic macular edema is a further complication of diabetes. It is an important type of diabetic eye disease and the main cause of blindness of diabetic patients. Qiming granule is a Chinese patent medicine widely used in the treatment of diabetic macular edema. There are some reports about this medicine for macular edema. At present, there is only 1 systematic review on qiming granule in the treatment of diabetic macular edema. However, there are many defects in this article, so it is necessary to re-summarize and evaluate the existing evidence. METHODS AND ANALYSIS: Three English database and 4 Chinese databases other sources will be searched. Two methodological trained researchers will read the title, abstract and full texts, and independently select the qualified literature according to inclusion and exclusion criteria. After assessment of the risk of bias and data extraction, we will conduct meta-analyses for outcomes including central macular thickness, optimum corrected vision, overall effect rates, and adverse effects. The heterogeneity of data will be investigated by Cochrane χ and I tests. We build 3 hypotheses for subgroup analysis according to the guidance for a credible subgroup effect: Disease status at baseline, duration of intervention, type of concomitant medication. Sensitivity analysis will be conducted to evaluate the stability of the results. Then publication bias assessment will be conducted by funnel plot analysis and Egger test. Finally, we will use the Grading of Recommendations Assessment, Development and Evaluate system to evaluate the quality of evidence. RESULTS: The results of our research will be published in a peer-reviewed journal. CONCLUSION: In our study, the evidence of qiming granule in the treatment of macular edema was comprehensively summarized and carefully evaluated. It will provide more options for clinical treatment of the disease. PROSPERO REGISTRATION NUMBER: CRD42018108626.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Edema Macular/tratamento farmacológico , Adulto , Idoso , Retinopatia Diabética/etiologia , Feminino , Humanos , Edema Macular/etiologia , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Revisão Sistemática como Assunto , Resultado do Tratamento
15.
BMC Ophthalmol ; 19(1): 200, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31519158

RESUMO

BACKGROUND: To compare the reoperation rate in patients with vitreous hemorrhage (VH) secondary to proliferative diabetic retinopathy (PDR) with or without preoperative intravitreal bevacizumab (IVB). METHODS: In this retrospective study, 280 patients (362 eyes) with diabetic VH were divided into a group that received preoperative IVB and a group that did not receive preoperative IVB. According to B-scan or color Doppler ultrasonography, the eyes were grouped as a VH group and a tractional retinal detachment (TRD) group. The reoperation rate, visual and anatomical outcomes of treatment were evaluated after 6 months. RESULTS: There were 17.4% of eyes in the VH group that did not receive preoperative IVB later required additional vitrectomy, while only 7.7% of the eyes in the VH group that received preoperative IVB required additional vitrectomy (P = 0.025). There were 45.5% of eyes in the TRD group that did not receive preoperative IVB had no reoperation, while only 21.4% of the eyes in the TRD group that received preoperative IVB had no reoperation (P = 0.004). The patients with one operation achieved better vision than those required reoperations in the VH group (P = 0.038) and TRD group (P = 0.019). CONCLUSIONS: Preoperative IVB significantly reduced the re-vitrectomy rate in patients with VH without TRD, but there was an increase in the reoperation rate in patients with VH combined with TRD.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Retinopatia Diabética/terapia , Vitrectomia , Hemorragia Vítrea/terapia , Idoso , Terapia Combinada , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/fisiopatologia , Retinopatia Diabética/cirurgia , Feminino , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Reoperação , Descolamento Retiniano/cirurgia , Estudos Retrospectivos , Ultrassonografia Doppler em Cores , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia , Hemorragia Vítrea/tratamento farmacológico , Hemorragia Vítrea/fisiopatologia , Hemorragia Vítrea/cirurgia
16.
Graefes Arch Clin Exp Ophthalmol ; 257(11): 2429-2436, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31512044

RESUMO

PURPOSE: Diabetic retinopathy (DR) is a complex eye disease associated with diabetes mellitus. It is characterized by three pathophysiological components, namely microangiopathy, neurodegeneration, and inflammation. We recently reported that intraperitoneal administration of BNN27, a novel neurosteroidal microneurotrophin, reversed the diabetes-induced neurodegeneration and inflammation in rats treated with streptozotocin (STZ), by activating the NGF TrkA and p75 receptors. The aim of the present study was to investigate the efficacy of BNN27 to protect retinal neurons when applied topically as eye drops in the same model. METHODS: The STZ rat model of DR was employed. BNN27 was administered as eye drops to diabetic Sprague-Dawley rats for 7 days, 4 weeks post-STZ (70 mg/kg) injection. Immunohistochemistry and western blot analyses were employed to examine the viability of retinal neurons in control, diabetic, and diabetic-treated animals and the involvement of the TrkA receptor and its downstream signaling ERK1/2 kinases, respectively. RESULTS: BNN27 reversed the STZ-induced attenuation of the immunoreactive brain nitric oxide synthetase (bNOS)- and tyrosine hydroxylase (TH)-expressing amacrine cells and neurofilament (NFL)-expressing ganglion cell axons in a dose-dependent manner. In addition, BNN27 activated/phosphorylated the TrkA receptor and its downstream prosurvival signaling pathway, ERK1/2 kinases. CONCLUSIONS: The results of this study provide solid evidence regarding the efficacy of BNN27 as a neuroprotectant to the diabetic retina when administered topically, and suggest that its pharmacodynamic and pharmacokinetic profiles render it a putative therapeutic for diabetic retinopathy.


Assuntos
Desidroepiandrosterona/administração & dosagem , Diabetes Mellitus Experimental , Retinopatia Diabética/tratamento farmacológico , Retina/patologia , Administração Tópica , Animais , Western Blotting , Desidroepiandrosterona/farmacocinética , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/metabolismo , Relação Dose-Resposta a Droga , Feminino , Masculino , Ratos , Ratos Sprague-Dawley , Retina/efeitos dos fármacos , Retina/metabolismo , Resultado do Tratamento
17.
Expert Opin Investig Drugs ; 28(10): 861-869, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31513439

RESUMO

Introduction: The Tie-2/Angiopoietin pathway is a therapeutic target for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Activation of Tie-2 receptor via Ang-1 maintains vascular stability to limit exudation. Ang-2, a competitive antagonist to Ang-1, and VE-PTP, an endothelial-specific phosphatase, interfere with the Tie-2-Ang-1 axis, resulting in vascular leakage. Areas covered: Faricimab, a bispecific antibody that inhibits VEGF-A and Ang-2, is in phase 3 trials for nAMD and DME. Nesvacumab is an Ang-2 inhibitor; when coformulated with aflibercept, it failed to show benefit over aflibercept monotherapy in achieving visual gains in phase 2 studies of nAMD and DME. ARP-1536 is an intravitreally administered VE-PTP inhibitor undergoing preclinical studies. AKB-9778 is a subcutaneously administered VE-PTP inhibitor that, when combined with monthly ranibizumab, reduced DME more effectively than ranibizumab monotherapy in a phase 2 study. AKB-9778 monotherapy did not reduce diabetic retinopathy severity score compared to placebo. AXT107, currently in the preclinical phase, promotes conversion of Ang-2 into a Tie-2 agonist and blocks signaling through VEGFR2 and other receptor tyrosine-kinases. Expert opinion: Tie-2/Angiopoietin pathway modulators show promise to reduce treatment burden and improve visual outcomes in nAMD and DME, with potential to treat cases refractory to current treatment modalities.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Retinopatia Diabética/tratamento farmacológico , Degeneração Macular/tratamento farmacológico , Inibidores da Angiogênese/farmacologia , Angiopoietina-1/antagonistas & inibidores , Angiopoietina-2/antagonistas & inibidores , Animais , Retinopatia Diabética/fisiopatologia , Humanos , Degeneração Macular/fisiopatologia , Edema Macular/tratamento farmacológico , Edema Macular/fisiopatologia , Receptor TIE-2/efeitos dos fármacos , Receptor TIE-2/metabolismo , Transdução de Sinais/efeitos dos fármacos
18.
Acta Diabetol ; 56(12): 1341-1350, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31541334

RESUMO

AIMS: To provide 2-year follow-up data on eyes with diabetic macular edema (DME) that were non-responsive after three initial anti-vascular endothelial growth factor (VEGF) injections, comparing functional and anatomical outcomes under continued anti-VEGF therapy versus dexamethasone (DEX) implant. METHODS: Multicenter, retrospective chart review comparing eyes with treatment-naïve DME and a suboptimal response to a loading phase of anti-VEGF therapy (3 injections given monthly) which were then treated with (a) further anti-VEGF (n = 72) or (b) initially switched to DEX implant (n = 38). Main outcome measures were change in visual acuity (VA) and central subfield thickness (CST) from the end of the loading phase to 24 months. RESULTS: In 79% of the 12-month study population (87/110 eyes), 24-month data were available. One quarter of eyes in each group switched treatments during the second year. Eyes that were switched early to DEX implant maintained the functional and anatomical improvements at 24 months which were seen in the first year (from month 3: + 8.9 letters, - 214 µm). Eyes that were switched from anti-VEGF therapy to steroids in the second year improved VA and reduced CST at 24 months (from month 12: + 6.8 letters, p = 0.023; - 226 µm, p = 0.004). In eyes continued on anti-VEGF therapy, VA and CST were stable at 24 months (from month 3: + 2.8 letters, p = 0.254; - 24 µm, p = 0.243). Eyes that were non-responsive to anti-VEGF therapy for 12 months had similar chances to experience a VA gain from further therapy as eyes that were non-responsive for 3 months only (23.8 vs. 31.0%, p = 0.344). CONCLUSIONS: The beneficial effect of an early switch to DEX implant in DME non-responders seen at month 12 was maintained during the second year. A later switch from anti-VEGF to steroids still provided significant improvement. Eyes continued on anti-VEGF over a period of 24 months maintained vision. A quarter of eyes, which had not improved vision at 12 months, exhibited a delayed response to treatment.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Dexametasona/administração & dosagem , Retinopatia Diabética/tratamento farmacológico , Edema Macular/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Idoso , Bevacizumab/administração & dosagem , Retinopatia Diabética/epidemiologia , Esquema de Medicação , Implantes de Medicamento , Resistência a Medicamentos/efeitos dos fármacos , Substituição de Medicamentos , Feminino , Humanos , Injeções Intravítreas , Edema Macular/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/imunologia , Acuidade Visual/efeitos dos fármacos
19.
Mater Sci Eng C Mater Biol Appl ; 105: 110092, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31546391

RESUMO

Naltrexone (NTX) is a potent opioid growth factor receptor (OGFR) antagonist proved to be useful for treatment of ocular surface complications. The aim of this work was to explore the feasibility of designing NTX-imprinted 2-hydroxyethyl methacrylate-based hydrogels for sustained drug release on the ocular surface. Acrylic acid (AAc) and benzyl methacrylate (BzMA) were chosen as functional monomers able to form binding cavities mimicking OGFR binding sites for NTX. Imprinted hydrogels containing functional monomers loaded higher amounts of NTX compared to non-imprinted ones by simple soaking in drug aqueous solution. In addition, possibility of carrying out the loading and sterilization processes in one step was investigated. NTX release was evaluated both under agitated sink conditions and in a microfluidic flow chamber mimicking the hydrodynamic conditions of the eye, namely the small volume of lachrymal fluid and its renovation rate. Sustained release profiles together with adequate swelling degree (46 to 57% w/w), light transparency (over 85%) and oxygen permeability may make these hydrogels suitable candidates to NTX-eluting contact lenses. NTX-loaded and non-loaded discs successfully passed the chorioallantoic membrane test for potential ocular irritation and were cytocompatible with human mesenchymal stem cells. Finally, NTX-imprinted hydrogels tested in the bovine corneal permeability assay provided therapeutically relevant amounts of NTX inside the cornea, reaching drug levels similar to those attained with a concentrated aqueous solution in spite the discs showed sustained release.


Assuntos
Córnea/metabolismo , Retinopatia Diabética/tratamento farmacológico , Hidrogéis , Naltrexona , Animais , Bovinos , Embrião de Galinha , Córnea/patologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Humanos , Hidrogéis/química , Hidrogéis/farmacocinética , Hidrogéis/farmacologia , Naltrexona/química , Naltrexona/farmacocinética , Naltrexona/farmacologia , Permeabilidade
20.
Int J Nanomedicine ; 14: 6357-6369, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496691

RESUMO

Background: Diabetic retinopathy (DR) is a complication of diabetes that affects the eyes and vision. It is a leading cause of visual impairment and blindness in working-age people. Vascular endothelial growth factor-A (VEGF-A) is a primary initiator and potential mediator of DR. Matrix metalloproteinase-9 (MMP-9) plays a progressive role in the onset and severity of DR. Interleukin-12 (IL-12) is a cytokine of the chemokine family that could reduce the levels of MMP-9 and VEGF-A and suppress tumor angiogenesis. We hypothesize that IL-12 may also have superior therapeutic efficacy against DR. However, protein drugs are prone to degradation by various proteases after drug injection. Therefore, they have short half-lives and low blood concentrations. The objective of this study was to develop IL-12-loaded nanoparticles for long-term and sustained DR treatment. Methods: IL-12-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (IL-12-PNP) were developed by double emulsion. The characteristics, anti-DR activity, and mechanisms of IL-12-PNP were examined in vitro and in vivo. Results: The nanoparticles had suitable particle size (~132.8 nm), drug encapsulation efficiency (~34.7%), and sustained drug release profile. Compared with IL-12 and blank nanoparticles, IL-12-PNP showed better inhibitory efficacy against VEGF-A and MMP-9 expression in rat endothelial cells and DR mouse retina. Intraocular IL-12-PNP administration significantly reduced retinal damage in DR mice as they presented with increased thickness and decreased neovascularization after treatment. Conclusion: These data indicate that IL-12-PNP is an effective drug delivery platform for DR therapy. It restores the thickness and reduces neovascularization of the retinas of DR mice.


Assuntos
Retinopatia Diabética/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Interleucina-12/administração & dosagem , Interleucina-12/uso terapêutico , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Animais , Preparações de Ação Retardada/farmacologia , Retinopatia Diabética/patologia , Células Endoteliais/metabolismo , Injeções Intravítreas , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Nanopartículas/ultraestrutura , Neovascularização Patológica/tratamento farmacológico , Ratos Sprague-Dawley , Retina/efeitos dos fármacos , Retina/metabolismo , Retina/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
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