Influence of ranibizumab treatment on the extracellular matrix in patients with neovascular age-related macular degeneration

Nita, Małgorzata; Michalska-Małecka, Katarzyna; Mazurek, Urszula; Kimsa, Malgorzata W.; Strzałka‐Mrozik, Barbara; Grzybowski, Andrzej; Romaniuk, Dorota

doi:10.12659/msm.890031

Cited by 6 publications

(2 citation statements)

References 63 publications

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“…ECM is a highly dynamic composition of vasculature [ 6 ]. Collagen is the most abundant protein in the ECM [ 7 ]. It has been shown that accumulation of ECM is one of the most notable pathologic changes across the vascular wall in pulmonary hypertension [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Activation of AMPK Prevents Monocrotaline-Induced Extracellular Matrix Remodeling of Pulmonary Artery

Han

Zhang

et al. 2016

Med Sci Monit Basic Res

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BackgroundThe current study was performed to investigate the effect of adenosine monophosphate (AMP) – activated protein kinase (AMPK) activation on the extracellular matrix (ECM) remodeling of pulmonary arteries in pulmonary arterial hypertension (PAH) and to address its potential mechanisms.Material/MethodsPAH was induced by a single intraperitoneal injection of monocrotaline (MCT) into Sprague-Dawley rats. Metformin (MET) was administered to activate AMPK. Immunoblotting was used to determine the phosphorylation and expression of AMPK and expression of tissue inhibitor of metalloproteinase-1 (TIMP-1). Gelatin zymography was performed to determine the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9.ResultsActivation of AMPK by MET significantly reduced the right ventricle systolic pressure and the right ventricular hypertrophy in MCT-induced rat PAH model, and partially inhibited the ECM remodeling of pulmonary arteries. These effects were coupled with the decrease of MMP-2/9 activity and TIMP-1 expression.ConclusionsThis study suggests that activation of AMPK benefits PAH by inhibiting ECM remodeling of pulmonary arteries. Enhancing AMPK activity might have potential value in clinical treatment of PAH.

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Section: Introductionmentioning

confidence: 99%

Activation of AMPK Prevents Monocrotaline-Induced Extracellular Matrix Remodeling of Pulmonary Artery

Han

Zhang

et al. 2016

Med Sci Monit Basic Res

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“…Age-related macular degeneration (AMD) is the main cause of practical and irreversible central blindness in patients after the age of 50 years [ 5 , 6 ]. Neovascular age-related macular degeneration, also known as exudative AMD, has a long natural course that involves repeated haemorrhages in the macular area and a poor prognosis in terms of visual acuity.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of Intravitreal Injection of Ranibizumab for Neovascular Age-Related Macular Degeneration with Serous Pigment Epithelial Detachment

Zhang

Chen

et al. 2016

Med Sci Monit

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BackgroundWe sought to observe the effectiveness of intravitreal injection of ranibizumab in treating neovascular age-related macular degeneration (nAMD) with serous pigment epithelial detachment (sPED).Material/MethodsA retrospective, noncomparative case series was performed. Twenty-3 eyes of 23 patients with sPED secondary to nAMD who had received intravitreal injections of ranibizumab were included in this study. All patients underwent best-corrected visual acuity (BCVA), synchronous fluorescein fundus angiography (FFA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT) examinations. All patients were treated with pro re nata intravitreal injections after 3 loading doses of ranibizumab and were followed up for 12 months. The differences in the BCVAs, maximum PED heights, PED volumes and CFTs of the affected eyes were compared between the baseline and last visit.ResultsTwelve months after the first injection, improved visual acuity was observed in 16 of the 23 eyes. 4 eyes exhibited stable visual acuity, and 3 eyes exhibited impaired visual acuity. The mean post-injection logMAR BCVA was 0.58±0.05, which was much better than that at baseline (0.76±0.08; t=1.751, P=0.0869). The mean maximum PED height at baseline was 350.17±35.73μm and it was decreased to 238.87±36.87μm (t=2.192, P=0.0337) at the last visit. The mean PED volume after injection was 0.34±0.1 mm3, which was significantly decreased compared with that at baseline (0.81±0.21 mm3; t=2.021, P=0.0494).The mean CFT decreased, but this difference was not statistically significant (t=1.003, P=0.3211). None of the patients exhibited endophthalmitis, uveitis or RPE tears.ConclusionsIntravitreal injection of ranibizumab for the treatment of neovascular age-related macular degeneration with serous pigment epithelial detachment safely and effectively improved the patients’ visual acuities and decreased their PED heights volumes.

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Suppression of aberrant choroidal neovascularization through activation of the aryl hydrocarbon receptor

Choudhary

Safe

Malek

2018

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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The aryl hydrocarbon receptor (AhR) is a ligand activated transcription factor, initially discovered for its role in regulating xenobiotic metabolism. There is extensive evidence supporting a multi-faceted role for AhR, modulating physiological pathways important in cell health and disease. Recently we demonstrated that the AhR plays a role in the pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly. We found that loss of AhR exacerbates choroidal neovascular (CNV) lesion formation in a murine model. Herein we tested the therapeutic impact of AhR activation on CNV lesion formation and factors associated with aberrant neovascularization. We screened a panel of synthetic drugs and endogenous AhR ligands, assessed their ability to activate AhR in choroidal endothelial cells, and inhibit angiogenesis in vitro. Drugs with an anti-angiogenic profile were then administered to a murine model of CNV. Two compounds, leflunomide and flutamide, significantly inhibited CNV formation concurrent with positive modifying effects on angiogenesis, inflammation, extracellular matrix remodeling, and fibrosis. These results validate the role of the AhR pathway in regulating CNV pathogenesis, identify mechanisms of AhR-based therapies in the eye, and argue in favor of developing AhR as a drug target for the treatment of neovascular AMD.

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Influence of ranibizumab treatment on the extracellular matrix in patients with neovascular age-related macular degeneration

Cited by 6 publications

References 63 publications

Activation of AMPK Prevents Monocrotaline-Induced Extracellular Matrix Remodeling of Pulmonary Artery

Activation of AMPK Prevents Monocrotaline-Induced Extracellular Matrix Remodeling of Pulmonary Artery

Effectiveness of Intravitreal Injection of Ranibizumab for Neovascular Age-Related Macular Degeneration with Serous Pigment Epithelial Detachment

Suppression of aberrant choroidal neovascularization through activation of the aryl hydrocarbon receptor

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