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At least 613 records · Page 34Linked to original sources
PubMed2003

[Angioproliferative retinal disease caused by ischemia].

Ischemia is a major stimulus for angiogenesis, a biological response mechanism that describes the formation of new blood vessels from existing vessels. An ischemic cell communicates with endothelial cells by soluble factors such as VEGF (vascular endothelial growth factor) and its receptors. A major transcriptional factor for VEGF is HIF-1 (hypoxia inducible factor). Proliferation of endothelial cells alone does not result in stable vascular tubes, this is only achieved by recruiting additional cells such as pericytes. The stabilisation and destabilisation of vessels, which are important prerequisites for vascular growth, are in a dynamic equilibrium which can be modified by additional growth factors such as angiopoietins. In this review we discuss some of the molecular mechanisms leading from ischemia to proliferative retinopathy with a special focus on retinopathy of prematurity and the closely related mouse model of hyperoxia-induced retinopathy. This model is very useful when developing new antiangiogenic therapies based on the increasing understanding of the molecular pathogenesis of ischemic proliferative retinopathy.

Animals↗
PubMed2003

[Retinal vein occlusions].

There are still gaps in understanding the etiology and pathogenesis of circulatory disorders of the central retinal vein. Although various new therapeutic approaches have been developed in the past few years, existing therapy forms are subject to controversy and available data are to some extent inconsistent. This discussion in the German-language literature is associated with varied and nonuniform terminology, which should do justice in particular to concepts of pathomechanism and degree of specificity. The general designation, "occlusion" seems to be the most suitable of all available terms since this implies no conclusions on possible etiological factors. Retinal vein occlusions develop at different sites and to varying extents. Depending on t he location of the occlusion, they can be classified into occlusions of the central vein, hemicentral vein, major branch vein, and macular branch vein. This overview provides information on the current knowledge of the pathogenesis and both established approaches and those in ongoing clinical trials for the treatment of central venous and branch vein occlusions.

Diagnosis, Differential↗
PubMed2006

Recombinant alpha2(IV)NC1 domain of type IV collagen is an effective regulator of retinal capillary endothelial cell proliferation and inhibits pre-retinal neovascularisation.

BACKGROUND: A recombinant form of the alpha2(IV)NC1 domain of type IV collagen has been shown to have potent anti-angiogenic activity although this peptide has not been studied in the context of proliferative retinopathies. In the current investigation we examined the potential for alpha2(IV)NC1 to regulate retinal microvascular endothelial cell function using a range of in vitro and in vivo assay systems. MATERIALS AND METHODS: alpha2(IV)NC1 at concentrations between 0.1 and 1 mug/ml was added to retinal microvascular endothelial cells (RMECs) followed by assessment of cell attachment, proliferation and survival. This agent was also tested within a novel in vitro three-dimensional retinal angiogenesis assay and the number of angiogenic sprouts quantified. alpha2(IV)NC1 was also delivered intra-vitreally to mice with oxygen-induced proliferative retinopathy (OIR) and neovascularisation evaluated in comparison with vehicle-treated controls. RESULTS: RMECs treated with alpha2(IV)NC1 (0.1, 0.5 and 1 microg/ml) showed delayed attachment at 3 h post-seeding, although this deficit had been restored at the 6-h time point. BrdU assay of DNA replication revealed that confluent RMECs treated with alpha2(IV)NC1 showed no measurable response in comparison with vehicle-treated controls. By contrast, proliferation of sub-confluent RMECs was significantly reduced by alpha2(IV)NC1 at 0.5 microg/ml (P<0.01). alpha2(IV)NC1 also induced apoptosis in RMECs and inhibited angiogenesis of pre-existing retinal vascular networks in vitro (P<0.001). Intra-vitreal injection of alpha2(IV)NC1 in the OIR model significantly inhibited pre-retinal neovascularisation compared with vehicle-treated controls (P<0.001). CONCLUSION: alpha2(IV)NC1 inhibits angiogenesis in the retinal microvasculature. This recombinant protein has potential for the treatment of neovascularisation in proliferative retinopathies.

Animals↗
PubMed2006

Up-regulation of HIF-1alpha and VEGF expression by elevated glucose concentration and hypoxia in cultured human retinal pigment epithelial cells.

In order to explore the effect of high glucose concentration and high glucose concentration with hypoxia on the production of hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF), human RPE cells were cultured in 5.56 mmol/L glucose (control group), 5.56 mmol/L glucose with 150 micro mol/L CoCl2 (hypoxic group), 25 mmol/L glucose (high glucose group) and 25 mmol/L glucose with 150 micro mol/L CoCl2 (combination group). RT-PCR was used to detect the expression of HIF-1alpha and VEGF mRNAs. Western blot analysis was used to measure the levels of HIF-1alpha and VEGF proteins. Although the small amount of HIF-1alpha protein was able to be detected in high glucose group but not in control group, there was no significant difference between the expression of HIF-1alpha mRNA of RPE cells in high glucose group and that of RPE cells in control group. As compared with RPE cells in control group, the mRNA expression and the protein synthesis of VEGF in high glucose group were up-regulated. As compared with RPE cells in hypoxic group, the expression of HIF-1alpha mRNA of RPE cells in combination group was not different, but the protein synthesis of HIF-1alpha, the mRNA expression and the protein synthesis of VEGF were more obviously up-regulated. In conclusion, high concentration glucose mainly influence the protein synthesis of HIF-1alpha of RPE cell, and HIF-1alpha protein is able to be accumulated in high concentration glucose. Under hypoxia, the HIF-1alpha protein induced by high concentration glucose is more stable, and the expression of VEGF is obviously increased. It is suggested that high concentration glucose may play a role in retinal neovascularization, especially at ischemia stage of diabetic retinopathy.

Blotting, Western↗
PubMed1988

Prediction of coronary artery disease in a population of insulin-requiring diabetic patients: results of an 8-year follow-up study.

To identify predictors of clinical coronary artery disease, 110 insulin-requiring diabetic patients with no symptoms suggestive of cardiac disease and with a normal resting ECG underwent metabolic and noninvasive cardiovascular screening including a history and physical examination, exercise ECG, M-mode echocardiography, and chemical laboratory testing. During a median follow-up interval of 100 months, 14 of these patients had clinical evidence of coronary artery disease consisting of acute myocardial infarction, sudden cardiac death, or anginal chest pain with angiographic documentation of occlusive coronary artery disease. Baseline variables that were univariately predictive of subsequent clinical coronary disease included age, peak treadmill heart rate, and retinal neovascularization. According to multivariate analysis the peak treadmill heart rate was the single most important predictor of subsequent development of clinical coronary disease. A treadmill ECG result that was either abnormal or inconclusive because of failure to achieve 90% of predicted maximal heart rate identified each patient in whom clinical coronary artery disease developed within 50 months after entry testing. Thus the entry treadmill ECG provided prognostic information not available from the history and physical examination results, but little further prognostic information was provided after the first 50 months of follow-up, suggesting the need for serial testing.

Adolescent↗
PubMed1995

Intervention in diabetic vascular disease by modulation of growth factors.

Several growth factors have been implicated in the derangements of cellular metabolism and proliferation that occur in diabetes, eg. kidney mesangial expansion, retinal neovascular formation, and acceleration of atherosclerosis in large vessels. These phenomena contribute to the development and progression of diabetic microvascular and macrovascular disease. Pharmacological interventions aimed at reducing growth factor alterations, among other actions in diabetic vasculopathy, include a multitude of classes of drugs, such as angiotensin-converting enzyme (ACE) inhibitors, calcium antagonists, lipid-lowering drugs, and somatostatin analogs. New potential interventions, ie, antisense oligonucleotide local delivery, are being applied in growth factor research and may prove beneficial in diabetic macrovascular disease.

Arteriosclerosis↗
PubMed2005

New micro vertical scissors for the surgical ablation of retinal angiomatous proliferation.

PURPOSE: To develop new micro vertical scissors for the ablation of retinal angiomatous proliferation (RAP) to minimize possible retinal damage. DESIGN: Interventional case report. METHODS: New micro vertical scissors were developed and used for the ablation of RAP vessels. RESULTS: The length of the inner side of the tip is 180 microm, which is approximately one seventh that of regular vertical scissors. The scissors handled easily and the RAP vessels were ablated with less retinal damage compared with that associated with use of standard vertical scissors. Postoperatively, intraretinal hemorrhage was reduced and hyperfluorescence seen on indocyanine green angiography resolved. CONCLUSIONS: The new micro vertical scissors developed for the ablation of RAP vessels can be used safely and effectively during this surgical procedure.

Aged↗
PubMed2006

Pilot study on in vivo evaluation of retinal vascular maturity in newborn infants in the context of retinopathy of prematurity.

PURPOSE: To study the extent of retinal vascularization at birth. DESIGN: Prospective masked observational case series. METHODS: One hundred ten neonates, at different weeks of gestation and birth weights (BWs), had dilated fundus evaluation for zone of retinal vascularization by a masked observer. Maternal and neonatal factors were ascertained by a masked pediatrician. RESULTS: Irrespective of risk factors, eight of nine babies who were born at <30 weeks of gestation and at <1500 g BW had immature retina. Those babies who were born at >34 weeks of gestational age and at >1700 g BW had mature retina. Babies who were born between 31 to 34 weeks of gestation and at 1501 to 1700 g BW had variable extent of retinal vascularization at birth. Vascularization was affected by maternal anemia and the need for oxygen for >48 hours. CONCLUSION: There exists considerable variability in the extent of retinal vascularization in infants who are born between 31 to 34 weeks of gestation. Modifiable maternal and fetal factors could influence extent of this vascularization birth.

Birth Weight↗
PubMed2004

Integrin beta4 signaling promotes tumor angiogenesis.

Mice carrying a targeted deletion of the signaling portion of the integrin beta4 subunit display drastically reduced angiogenesis in response to bFGF in the Matrigel plug assay and to hypoxia in the retinal neovascularization model. Molecular cytology indicates that alpha6beta4 signaling promotes branching of beta4+ medium- and small-size vessels into beta4- microvessels without exerting a direct effect on endothelial cell proliferation or survival. Signaling studies reveal that alpha6beta4 signaling induces endothelial cell migration and invasion by promoting nuclear translocation of P-ERK and NF-kappaB. Upon subcutaneous implantation of various cancer cells, the mutant mice develop smaller and significantly less vascularized tumors than wild-type controls. These results provide genetic evidence that alpha6beta4 signaling promotes the onset of the invasive phase of pathological angiogenesis and hence identify a novel target for antiangiogenic therapy.

Animals↗
PubMed2004

Neuroprotective and antiangiogenic actions of PEDF in the eye: molecular targets and therapeutic potential.

Pigment epithelium-derived factor (PEDF) is a 50-kDa protein encoded by a single gene that shows strong conservation across phyla from fish to mammals. It is secreted by the retinal pigment epithelium (RPE) and a select number of other cell types in the eye, as well as by other tissues in the body. PEDF was originally defined by its ability to induce differentiation in retinoblastoma cells. It also promotes a non-proliferative, differentiated state in a number of other cell types. PEDF protects retinal neurons from light damage, oxidative stress and glutamate excitotoxicity. PEDF is also antiangiogenic and can inhibit the growth of blood vessels in the eye induced in a variety of ways. A balance in the levels of PEDF and the proangiogenic factor vascular endothelial growth factor-A is perturbed in a range of retinal neovascular diseases. Some of the pathways by which PEDF exerts its actions on cells have now been defined. Peptide fragments of PEDF carry biological activity and may be valuable therapeutic agents that readily penetrate the eye.

Amino Acid Sequence↗
PubMed2003

Angiogenic gene therapy with adenovirus 5 fibroblast growth factor-4 (Ad5FGF-4): a new option for the treatment of coronary artery disease.

Angiogenic gene therapy for stable angina is aimed at promoting new blood vessel formation in the heart, thus providing enhanced cardiac perfusion, symptom relief, increased exercise capacity, improved quality of life, and reduced risk of coronary events. Ad5FGF-4 is a replication-deficient serotype 5 adenovirus encoding the gene for fibroblast growth factor-4 (FGF-4) driven by a cytomegalovirus promoter. In preclinical studies using a pig model of myocardial ischemia, a single intracoronary infusion of Ad5FGF-4 improved cardiac contractile function and regional blood flow in the ischemic region during stress. These effects were apparent after 2 weeks and maintained for > or =12 weeks. Histologic evidence of capillary angiogenesis was observed. FGF-4 gene expression was detected in the heart but not at extracardiac sites. Placebo-controlled trials in humans with chronic stable angina indicate that Ad5FGF-4 increases treadmill exercise duration and improves stress-related ischemia measured by perfusion sestamibi single-photon emission computed tomography. More patients receiving Ad5FGF-4 than placebo reported complete resolution of their angina and no nitroglycerin use. Ad5FGF-4 gene therapy was well tolerated. The administration procedure did not cause any adverse events, although mild, transient fever, a transient modest fall in platelet count, and a transient mild elevation in hepatic enzymes and uric acid levels occurred in a few patients. This adverse event profile concurs with other adenoviral gene trials. There was no evidence of myocarditis, retinal neovascularization, or angioma formation. FGF-4 was not detected in venous blood. Larger clinical trials will assess Ad5FGF-4 with regard to cardiovascular prognosis, symptom relief, and safety profile in patients with chronic stable angina.

Adenoviridae↗
PubMed1995

Visual field loss after pars plana vitrectomy with air/fluid exchange.

PURPOSE: To report the postoperative finding of a dense, permanent, peripheral temporal visual field defect in the treated eyes of three patients who underwent pars plana vitrectomy with air/fluid exchange. METHODS: The patient's charts were reviewed. RESULTS: Visual field loss after pars plana vitrectomy and air/fluid exchange occurs and may be caused by mechanical trauma to the optic nerve head. CONCLUSION: Great caution is advised when aspirating directly over the optic nerve with any extrusion instrument.

Adult↗
PubMed1998

Cone b-wave implicit time as an early predictor of rubeosis in central retinal vein occlusion.

PURPOSE: To investigate the predictive value of the cone b-wave implicit time in the 30-Hz flicker electroretinogram for rubeosis in the acute phase of central retinal vein occlusion. METHODS: In a prospective study, 25 patients (25 eyes) with a central retinal vein occlusion of less than 14 days' duration were examined with electroretinography and followed up for a minimum of 18 months. RESULTS: The cone b-wave implicit time in the eyes that developed rubeosis (n = 11) was more than 37.1 milliseconds and in the eyes that did not develop rubeosis (n = 14), less than 37 milliseconds (P < .00001). CONCLUSION: The cone b-wave implicit time in the 30-Hz flicker electroretinogram is a good predictor of rubeosis at an early stage in eyes with central retinal vein occlusion.

Acute Disease↗
PubMed1996

Intravitreous injections of vascular endothelial growth factor produce retinal ischemia and microangiopathy in an adult primate.

PURPOSE: The purpose of the study is to determine the effect of exogenous vascular endothelial growth factor (VEGF) on the primate retina and its vasculature. METHODS: Ten eyes of five animals were studied. Physiologically relevant amounts of the 165 amino acid isoform of human recombinant VEGF were injected into the vitreous of six healthy cynomolgus monkey eyes. Inactivated human recombinant VEGF or vehicle was injected into four contralateral control subject eyes. Eyes were assessed by slit-lamp biomicroscopy, tonometry, fundus color photography, fundus fluorescein angiography, light microscopy, and immunostaining with antibodies against proliferating cell nuclear antigen and factor VIII antigen. RESULTS: All six bioactive VEGF-injected eyes developed dilated, tortuous retinal vessels that leaked fluorescein. Eyes receiving multiple injections of VEGF developed progressively dilated and tortuous vessels, venous beading, edema, microaneurysms, intraretinal hemorrhages and capillary closure with ischemia. The severity of the retinopathy correlated with the number of VEGF injections. None of the four control eyes exhibited any abnormal retinal vascular changes. The endothelial cells of retinal blood vessels were proliferating cell nuclear antigen positive only in the bioactive VEGF-injected eyes. CONCLUSION: Vascular endothelial growth factor is sufficient to produce many of the vascular abnormalities common to diabetic retinopathy and other ischemic retinopathies, such as hemorrhage, edema, venous beading, capillary occlusion with ischemia, microaneurysm formation, and intraretinal vascular proliferation.

Animals↗