scholarly journals Bumetanide Suppression of Angiogenesis in a Rat Model of Oxygen-Induced Retinopathy

2020 ◽  
Vol 21 (3) ◽  
pp. 987
Author(s):  
Sibel Guzel ◽  
Charles L. Cai ◽  
Taimur Ahmad ◽  
Michelle Quan ◽  
Gloria B. Valencia ◽  
...  

Aquaporins (AQPs) are involved in hypoxia-induced angiogenesis and retinal damage. Bumetanide is a diuretic agent, Na+/K+/Cl− cotransporter (NKCC1), and AQP 1–4 inhibitor. We tested the hypothesis that early postnatal treatment with bumetanide suppresses biomarkers of angiogenesis and decreases severe retinopathy oxygen-induced retinopathy (OIR). Neonatal rats were exposed at birth (P0) to either (1) room air (RA); (2) hyperoxia (50% O2); or (3) intermittent hypoxia (IH) consisting of 50% O2 with brief, clustered episodes of 12% O2 from P0 to postnatal day 14 (P14), during which they were treated intraperitoneally (IP) with bumetanide (0.1 mg/kg/day) or an equivalent volume of saline, on P0–P2. Pups were examined at P14 or allowed to recover in RA from P14–P21. Retinal angiogenesis, morphometry, pathology, AQPs, and angiogenesis biomarkers were determined at P14 and P21. Bumetanide reduced vascular abnormalities associated with severe OIR. This was associated with reductions in AQP-4 and VEGF. Bumetanide suppressed sVEGFR-1 in the serum and vitreous fluid, but levels were increased in the ocular tissues during recovery. Similar responses were noted for IGF-I. In this model, early systemic bumetanide administration reduces severe OIR, the benefits of which appear to be mediated via suppression of AQP-4 and VEGF. Further studies are needed to determine whether bumetanide at the right doses may be considered a potential pharmacologic agent to treat retinal neovascularization.

2019 ◽  
Vol 97 (4) ◽  
pp. 423-430 ◽  
Author(s):  
Shaoyang Shi ◽  
Yong Jin ◽  
Haishan Song ◽  
Xiaolong Chen

Pathological angiogenesis in the retina is one of the main ocular diseases closely associated with vision loss. This work investigated the roles of microRNA-34a (miR-34a) and its potential target Notch1, in retinal angiogenesis. For this we used oxygen-induced retinopathy (OIR) rats and human retinal microvascular endothelial cells (HRMECs) stimulated with vascular endothelial growth factor (VEGF). We performed hematoxylin–eosin staining, Western blot for VEGF, and immunofluorescence staining for CD31 to verify the establishment of our OIR model. We observed down-regulation of miR-34a, and up-regulation of Notch1 and Hey1 in retinas from OIR rats. We found similar results with the VEGF-stimulated HRMECs. By performing MTT assay, cell scratch assay, tube formation assay, and by detecting the expression of matrix-metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitors of metalloproteinases-1 (TIMP-1), and TIMP-2, we found that transfection of miR-34a ameliorated VEGF-mediated angiogenesis of HRMECs. We further observed that siRNA-induced gene silencing of Notch1 prevented VEGF-induced angiogenesis via regulating cell proliferation, cell migration, and tube formation of HRMECs. Additionally, activation of Notch1 by transfection of Notch1 plasmid attenuated the inhibitory effects of miR-34a on tube formation, in the present of VEGF. Results from our dual-luciferase reporter gene assay suggested that miR-34a targets Notch1. In summary, our data demonstrate that miR-34a attenuates retinal angiogenesis via targeting Notch1.


Antioxidants ◽  
2018 ◽  
Vol 7 (11) ◽  
pp. 160 ◽  
Author(s):  
Kay Beharry ◽  
Charles Cai ◽  
Faisal Siddiqui ◽  
Sara Chowdhury ◽  
Christina D’Agrosa ◽  
...  

Neonatal intermittent hypoxia (IH) or apnea afflicts 70% to 90% of all preterm infants <28 weeks gestation, and is associated with severe retinopathy of prematurity (ROP). We tested the hypotheses that coenzyme Q10 (CoQ10) or omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplementation during neonatal IH reduces the severity of oxygen-induced retinopathy (OIR). Newborn rats were exposed to two IH paradigms: (1) 50% O2 with brief hypoxia (12% O2); or (2) 21% O2 with brief hypoxia, until postnatal day 14 (P14), during which they received daily oral CoQ10 in olive oil, n-3 PUFAs in fish oil, or olive oil only and compared to room air (RA) treated groups. Pups were examined at P14, or placed in RA until P21. Retinal angiogenesis, histopathology, and morphometry were determined. Both IH paradigms produced severe OIR, but these were worsened with 50/12% O2 IH. CoQ10 and n-3 PUFAs reduced the severity of OIR, as well as ocular growth factors in both IH paradigms, but CoQ10 was more effective in 50/12% O2 IH. Supplementation with either CoQ10 or n-3 PUFAs targeting IH-induced retinal injury is individually effective for ameliorating specific characteristics consistent with ROP. Given the complexity of ROP, further studies are needed to determine whether combined CoQ10 and n-3 PUFAs supplementation would optimize their efficacy and result in a better outcome.


2021 ◽  
Vol 11 (2(40)) ◽  
pp. 64-67
Author(s):  
I.V. Lastivka ◽  
A.G. Babintseva ◽  
V.V. Antsupova ◽  
А.І. Peryzhniak ◽  
І.V. Koshurba ◽  
...  

Hemifacial Microsomia (HFM) is a term used to identify facial deformities associated with the development ofthe first and second pairs of branchial arches, characterized by underdevelopment of one half of the face. One typeof hemifacial microsomia is oculo-auriculo-vertebral dysplasia or Goldenhar syndrome.The incidence of HFM is 1:3500-1:7000 of live births and occurs in 1 case per 1000 children with congenitaldeafness. The ratio of boys to girls is 3:2. The etiology and type of inheritance is studied insufficiently. There are threepossible pathogenetic models: vascular abnormalities and hemorrhages in the craniofacial region, damage of Meckel'scartilage, and abnormal cell development of the cranial nerve crest. Environmental factors, maternal internal factors,and genetic factors (OTX2, PLCD3, and MYT1 mutations) may also cause the development of hemifacial microsomia.The article demonstrates a clinical case of hemifacial microsomia in a newborn boy from a mother with Z-21 inthe form of deformation of the left auricle with atresia of the auditory canal and "false" ears on the right, combinedwith congenital anomaly of heart (atrial septal defect) and brain (hypoplasia of the corpus callosum).Emphasis is placed on the need of involving a multidisciplinary team of specialists in the management of thispatient both in the neonatal period and in the system of subsequent follow-up.


2002 ◽  
pp. 303-309 ◽  
Author(s):  
A Colao ◽  
P Marzullo ◽  
G Lombardi

OBJECTIVE: To evaluate the effect of a 6-month treatment with slow-release lanreotide (LAN) on cardiovascular risk and atherosclerosis in 24 normotensive patients with active acromegaly (GH=67.4 +/- 12.6 mU/l, IGF--I=866.0 +/- 55.8 microg/l) and 24 healthy subjects sex-, age- and body mass index-matched with the patients (as controls). DESIGN: Open, prospective, multicenter. METHODS: The following were measured before and after 6 months of LAN treatment (dose 60-90 mg/month): fasting GH, IGF-I, LDL, HDL and total cholesterol, triglyceride, glucose, glycosylated hemoglobin, insulin and fibrinogen levels, intima-media thickness (IMT) and blood systolic and diastolic peak velocity (SPV and DPV respectively) in both common carotids. RESULTS: At study entry, insulin, total and LDL cholesterol, triglyceride and fibrinogen levels were higher while HDL cholesterol levels were lower in patients than in controls. At the right (0.88 +/- 0.04 vs 0.77 +/- 0.03 mm, P=0.05) and left (0.93 +/- 0.03 vs 0.78 +/- 0.02 mm, P=0.01) common carotid IMT was significantly higher in patients than in controls; 12 patients and two controls showed an IMT of > or = 1 mm (chi(2)=8.2, P=0.004). After 6 months of LAN treatment, disease control was achieved in 15 patients (62.5%). Insulin, triglyceride and fibrinogen levels were significantly decreased, and a trend toward a decrease of IMT in the right (from 0.90 +/- 0.05 to 0.78 +/- 0.04 mm, P=0.06) and left (from 0.95 +/- 0.04 to 0.84 +/- 0.04 mm, P=0.06) common carotid arteries was observed only in patients with disease control, while SPV and DPV did not change. CONCLUSIONS: LAN treatment for 6 months significantly lowered GH, IGF-I, insulin and fibrinogen levels and reduced IMT of both common carotid arteries in normotensive patients with acromegaly.


2018 ◽  
Vol 32 (2) ◽  
pp. 204-210 ◽  
Author(s):  
Hee Young Kim ◽  
Seung-Hoon Baek ◽  
Seong Wan Baik ◽  
Sun Sik Bae ◽  
Jung Min Ha ◽  
...  

PEDIATRICS ◽  
1949 ◽  
Vol 4 (6) ◽  
pp. 751-768
Author(s):  
HERBERT E. GRISWOLD ◽  
MAURICE D. YOUNG

The anatomic nature of a double aortic arch is described. Reference is made to the history of the malformation. The clinical picture and radiographic findings described by various authors are discussed. Two cases are reported which demonstrate two types of double aortic arch, One, a relatively common type, had a large right arch with a retro-esophageal component and a left descending aorta; the second, a rare type, had a large left arch with a retro-esophageal component and a right descending aorta. Further, one was an infant who had symptoms of constriction whereas the other was an adult who had no symptoms referable to the double aortic arch. Analysis is made of these cases and 47 other cases reported in the literature. This analysis reveals that: 1. There is a striking correlation between the occurrence of symptoms and the age and duration of life, but there is no correlation between the occurrence of symptoms and the type of double aortic. 2. A double aortic arch in which both components are patent throughout is more likely to produce symptoms than a double aortic arch in which one component is partially obliterated. The process of obliteration does not appear to give rise to symptoms. 3. There is considerable variation in the relative sizes of the components of a double aortic arch. The right component is usually the larger; part of the left component may be obliterated. To date, no case has been reported of obliteration of part of a persistent right Component. 4. A double aortic arch occurs more commonly with a left descending aorta than with a right descending aorta. 5. It is unusual for a double aortic arch to be associated with a malformation of the heart. The association of a double aortic arch with other vascular abnormalities is less rare. The two principal problems raised by the demonstration of a retro-esophageal vessel are discussed. The first concerns the nature of the malformation; the second concerns the advisability of operation in the given individual.


2019 ◽  
Vol 03 (04) ◽  
pp. 337-346
Author(s):  
Leah Braswell

AbstractThe imaging of the mesenteric vasculature of infants and children can be effectively accomplished using a variety of noninvasive and invasive techniques. As with adult imaging, the choice of modality will depend on the specific clinical scenario. Unique considerations and challenges are related to pediatric body size, pathology, the patient's developmental ability to tolerate the exam, and practical radiation concerns. Pediatric angiography can provide both diagnostic information and a pathway to definitive treatment of vascular abnormalities. Utilizing the right modality in the appropriate situation allows for accurate and timely diagnosis so that treatment is most effective.


2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Ali Nowrouzi ◽  
Javier Benitez-del-Castillo ◽  
Sepideh Kafi-abasabadi ◽  
Mario Rodriguez-Calzadilla ◽  
Antonio Diaz-Ramos ◽  
...  

Abstract Introduction Normal-tension glaucoma is known as a multifactorial optic neuropathy. A number of lines of evidence suggested that vascular factors played a significant role in the development of normal-tension glaucoma. The mechanisms underlying the abnormal ocular blood flow in normal-tension glaucoma are still not clear. Peripheral vascular disease seems to be associated with glaucoma populations independent of other cardiovascular risk factors. We found this presentation, for the first time, to our knowledge, as another probable vascular abnormality related to our patient with normal-tension glaucoma, although it is necessary to confirm its pathological effect in future studies. Case presentation Our patient was a 48-year-old Spanish man without any personal and family history of interest except for circulatory problems of the lower limbs with repetitive ulcers at the frontal and lateral aspects of his legs. His chief complaint was vision loss when he came to consult us. In exploration, his best corrected visual acuity was 20/20 in both eyes; initial intraocular pressure in the right eye was 14–16 mmHg and in the left eye was 16–18 mmHg, with a mild sclerosis of the lens in slit-lamp examination. No inflammation or pigmented lesion was detected in the anterior chamber. Open angle confirmed by Goldman four quadrants gonioscopy. Funduscopic examination revealed a vertical cup disc ratio of 0.6 in the right eye and 0.8 in the left eye. The patient’s neuroretinal rim was normal in the right eye, and superior thinning in the left eye was determined. Examination of the patient’s visual field showed inferior mild probable nasal scotoma in the right eye and an inferior deep arcuate scotoma defect in the left eye. His optical coherence tomography examination revealed thinning of the peripapillary nerve fiber layer thickness in the left eye and superior loss of macular retinal ganglion cells in the left eye. Normal intraocular pressure values were measured on the intraocular pressure curve without treatment (maximum value, 18–20 mmHg), discarding higher intraocular pressures measured out of office. Ultrasonic pachymetry measured 515/520 μm, and normal intraocular pressure measured with a PASCAL tonometer ruled out probable corneal biomechanical underestimations. The patient’s polysomnography study was normal and excluded sleep apnea syndrome. The patient’s serial mean blood pressure was normal, especially in the lower limbs (mean value, 125/70 mmHg), ruling out the possibility of systemic hypotension. Thyroidal and coagulation abnormalities, autoimmune disease, and inflammatory disease were excluded. Normal immunologic study and normal vascular biopsy were observed, as well as normal brain magnetic resonance imaging and a normal carotid vascular study. The primary diagnosis was moderate medium peripheral arterial disease in the lower limbs, which was confirmed by echography after ruling out other probable vascular abnormalities related to normal-tension glaucoma. Conclusion After ruling out other systemic diseases and vascular abnormalities related to normal-tension glaucoma, we found peripheral arterial disease as a probable vascular abnormality related to normal-tension glaucoma in our patient. To our knowledge, this is the first time such a case has been reported. Thus, further research is needed to determine the relevance of these results to the general population.


2014 ◽  
Vol 92 ◽  
pp. 0-0
Author(s):  
M DAL MONTE ◽  
GP NICCHIA ◽  
M CAMMALLERI ◽  
IA FRIGERI ◽  
I FORNACIARI ◽  
...  

2020 ◽  
pp. 112067212094657
Author(s):  
Dario Pasquale Mucciolo ◽  
Vittoria Murro ◽  
Dario Giorgio ◽  
Andrea Sodi ◽  
Ilaria Passerini ◽  
...  

Purpose: To report a case of choroideremia characterized by peripheral retinoschisis with vascular abnormalities and vitreous hemorrhage. Observations: A 58-year-old man affected by advanced-stage choroideremia was diagnosed with peripheral retinoschisis in both eyes. Vitreous hemorrhage was present in the right eye with a peculiar clot-like lesion at the periphery. At the 1-year follow-up, the vitreous hemorrhage had reabsorbed and the vascular clot-like lesion in the periphery had almost completely disappeared. Conclusion and importance: We have reported fundoscopic and OCT features of peripheral-acquired retinoschisis with vascular abnormalities in a patient with choroideremia. OCT examination is extremely useful in clinical evaluation of the peripheral retinal alterations in these cases, where the absence of the retinal pigment epithelium and the choriocapillaris pose many diagnostic difficulties.


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