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Results for “Retinal Neovascularization”

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At least 127 records · Page 7Linked to original sources
PubMed2005

Inhibition of pathologic retinal neovascularization by alpha-defensins.

Proliferative retinopathies, such as those complicating prematurity and diabetes, are major causes of blindness. A prominent feature of these retinopathies is excessive neovascularization, which is orchestrated by the hypoxia-induced vascular endothelial growth factor (VEGF) stimulating endothelial cells and the integrin-mediated adhesive interactions of endothelial cells with extracellular matrix components such as fibronectin (FN). Recently, we demonstrated that alpha-defensins interfere with alpha5beta1-FN interactions and dependent endothelial cell functions. Here, alpha-defensins were studied in hypoxia-induced proliferative retinopathy. In vitro, alpha-defensins specifically inhibited alpha5beta1-integrin-dependent migration of bovine retinal endothelial cells (BRECs) to FN, attenuated the VEGF-stimulated increase in endothelial permeability, and blocked BREC proliferation and capillary sprout formation in 3-dimensional fibrin-matrices. An up-regulation of beta1-integrin and FN was observed in the retinal vessels in the mouse model of hypoxia-induced retinal angiogenesis. Systemic and local administration of alpha-defensins reduced retinal neovascularization by 45% and 60%, respectively, and this effect was comparable to the inhibitory effect of alpha5beta1-blocking antibody. alpha-Defensins were detected in human diabetic retinas associated with normal retinal vessels but were absent from proliferative lesions. Together, these data show that alpha-defensins inhibit pathologic retinal neovascularization in vivo and may provide a clinically efficient strategy against proliferative retinopathies.

Animals↗
PubMed2004

Effect of methylimidazole-induced hypothyroidism in a model of low retinal neovascular incidence.

PURPOSE: To determine the effect of methylimidazole (MMI)-induced hypothyroidism in a newborn rat model of low retinal neovascular (NV) incidence. METHODS: Control and MMI-exposed newborn rats were raised either in room air or variable oxygen (40/15) until P14. All groups were then exposed to room air between postnatal day (P)14 and P20. Dams drank either tap water or water containing MMI. Eyes of animals in all groups were enucleated, and retinas were removed and stained with adenosine diphosphatase and analyzed for peripheral avascularity, vascular density, and NV incidence and severity. RESULTS: In the control group, MMI treatment did not promote the development of retinal NV although a linear relationship (r = 0.99, P < 0.01) was found between increased MMI dose and lower peripheral retinal vascular densities. In all the 40/15 groups, peripheral retinal vascular densities were lower (P < 0.05) than normal and were not a function of MMI dose. Increased MMI dose produced increased retinal incidence of NV (r = 0.99, P < 0.05). CONCLUSIONS: These data are consistent with the notions that thyroid function contributes to normal retinal vascular density and that hypothyroidism can play a permissive role in the development of retinal NV.

Adenosine Diphosphate↗
PubMed2002

Somatostatin analogs inhibit neonatal retinal neovascularization.

The goal of this study was to determine the effect of two somatostatin analogs, Woc4D and octreotide, on oxygen induced retinopathy in the mouse. Oxygen induced retinopathy was produced in C57BL6 mice. Octreotide and Woc4D were administered from post-natal day 12-16. Retinopathy was assessed by a retinal scoring system utilizing fluorescein perfused retinal whole mounts. Animals treated with Woc4D and octreotide, respectively, had median retinopathy scores of 4(3,5) [median(25th, 75th quartile)] with P = 0.01 and 3.5(2.9,4.3) with P = 0.01 compared to oxygen and sham treated oxygen animals with scores of 6.6(5.3,8.5) and 7.4(5.8,8.6), respectively. Woc4D and octreotide treated animals had decreased blood vessel tufts and decreased extra-retinal neovascularization when compared to oxygen treated animals. Pituitary growth hormone (GH) mRNA expression was increased 8.3-fold by Woc4D treatment and 106-fold by oxygen exposure, and GH and mRNA was markedly reduced by Woc4D as well as octreotide. Growth as measured by animal weight was unaffected by either treatment. Woc4D and octreotide inhibited retinal neovascularization in an equally effective manner in the mouse model of oxygen induced retinopathy.

Angiogenesis Inhibitors↗
PubMed1977

Peripheral retinal neovascularization in sarcoidosis and sickle cell anemia.

A 30-year-old black woman with biopsy-proven sarcoidosis and sickle cell anemia had peripheral retinal neovascularization. Elevated fibrovascular proliferations and distal retinal ischemia with nonperfused ghost vessels passing through the area of neovascularization were found at the temporal periphery. No signs of intraocular inflammation were present. Both diseases occur in black patients and should always be considered in the presence of peripheral retinal neovascularization.

Adult↗
PubMed2004

Transcription factor Ets-1 mediates ischemia- and vascular endothelial growth factor-dependent retinal neovascularization.

Transcription factor Ets-1 has been reported to regulate angiogenesis in vascular endothelial cells. Here, we investigated a mechanism that may regulate the expression of Ets-1 in vascular endothelial growth factor (VEGF)- and hypoxia-induced retinal neovascularization and that may have potential to inhibit ocular neovascular diseases. VEGF and hypoxia increased Ets-1 expression in cultured bovine retinal endothelial cells. The VEGF-induced mRNA increase of Ets-1 was suppressed by a tyrosine kinase inhibitor (genistein), by inhibitors of MEK (mitogen-activated protein and extracellular signal-regulated kinase kinase) (PD98059 and UO126), and by inhibitors of protein kinase C (GF109203X, staurosporine, and Gö6976). Dominant-negative Ets-1 inhibited VEGF-induced cell proliferation, tube formation, and the expression of neuropilin-1 and angiopoietin-2. In a mouse model of proliferative retinopathy, Ets-1 mRNA was up-regulated. Intravitreal injection of dominant-negative Ets-1 suppressed retinal angiogenesis in a mouse model of proliferative retinopathy. In conclusion, VEGF induces Ets-1 expression in bovine retinal endothelial cells and its expression is protein kinase C/ERK pathway-dependent. Ets-1 up-regulation is involved in the development of retinal neovascularization, and inhibition of Ets-1 may be beneficial in the treatment of ischemic ocular diseases.

Adenoviridae↗
PubMed2003

Inhibition of retinal neovascularization by intravitreal injection of human rPAI-1 in a rat model of retinopathy of prematurity.

PURPOSE: Restructuring of extracellular matrix at actively extending blood vessel tips involves secretion of plasminogen activator (PA). Findings in earlier studies conducted in the authors' laboratory have suggested that angiostatic steroids suppress the PA activity essential for the invasive aspect of angiogenesis by increasing synthesis of plasminogen activator inhibitor (PAI)-1. This experiment was designed to test the effect of administration of exogenous PAI-1 on retinal neovascularization (NV) in an animal model of retinopathy of prematurity (ROP). METHODS: At birth, Sprague-Dawley rats were placed into incubators and exposed to an atmosphere alternating between 50% and 10% O(2) every 24 hours. After 14 days, the animals were removed to room air, at which time each received a single intravitreal injection of 5 microL of buffer vehicle or one of five doses of PAI-1, ranging from 3.0 microg/mL to 2.0 mg/mL. Animals were killed 6 days later, and retinal NV was assessed using adenosine diphosphatase (ADPase) histochemical staining. RESULTS: Retinal neovascularization decreased with increasing PAI-1 dosage. The most effective dose tested (2.0 mg/mL) caused a 52% reduction in retinal NV relative to vehicle (P < 0.005). Normal vasculogenesis, as determined by measuring retinal vascular area, was unaffected. CONCLUSIONS: PAI-1 inhibits pathologic angiogenesis without adversely affecting normal vasculogenesis, an attractive feature for ROP therapies. Moreover, PAI's relationship to matrix metalloproteinases, which are also implicated in angiogenesis, suggests that the proteolytic aspect of the process may provide additional downstream therapeutic targets.

Animals↗
PubMed2001

Variable supplemental oxygen during recovery does not reduce retinal neovascular severity in experimental ROP.

PURPOSE: To test the hypothesis that variable supplemental oxygen (VSO) during recovery is not as effective as constant supplemental oxygen treatment at reducing retinal neovascular severity in the newborn rat model of retinopathy of prematurity (ROP). METHODS: The ROP model consists of raising newborn rats in variable oxygen for 14 days and then allowing them to recover during the next 6 days (until day 20). During this recovery period, two VSO protocols were examined: 1) 24 hr cycled (28% for 24 hr and 21% for 24 hr) as a control, and 2) interrupted (28% for 23.75 hr and 21% for 0.25 hr). On day 20, retinas from both eyes of each animal were dissected, stained with ADPase, and analyzed for neovascular (NV) incidence, severity, and peripheral avascularity. RESULTS: No significant differences (P > 0.05) in NV incidence and severity were found between the 24 hr cycled (control) (95% (38/40), median 5 clockhrs, range 0.5-9, n = 38) and interrupted VSO groups (89% (40/45), 3.5 clockhrs, 0.5-10.5, n = 40). However, retinal NV severity from both VSO groups were significantly greater (P < 0.05) than that previously reported for constant supplemental oxygen treatment. Percent peripheral avascularities were not significantly different (P > 0.05) between the two VSO groups. CONCLUSIONS: These results support our hypothesis since both VSO conditions were significantly less effective at reducing retinal NV than constant supplemental oxygen during recovery. The possible application of these results to STOP-ROP trial is discussed.

Animals↗
PubMed1977

Experimental retinal neovascularization induced by intravitreal tumors.

Adult rabbit retinal vessels underwent neovascularization in response to tumor implantation within the vitreous body. The neovascular response was presumably elicited by the tumor angiogenesis factor (TAF). The response of adult retinal vessels to an angiogenic stimulus raises the possibility that a similar substance may cause retinal neovascularization in humans, and that in normal conditions the vitreous may be able to suppress angiogenic activity.

Angiogenesis Inducing Agents↗
PubMed2004

[The inhibitory effects of angiostatin on retinal neovascularization induced by oxygen].

OBJECTIVE: To observe the inhibitory effects of angiostatin on microvascular endothelial cells of mouse retina and test the efficacy of native angiostatin in suppressing experimental retinal neovascularization induced by oxygen. METHODS: Angiostatin was purified with L-lysine Sepharose 4B from human plasma. The primary microvascular endothelial cells from rat retina were cultured. Microvascular endothelial cells growth inhibition assay was carried out with MTT method. Mouse models of hyperoxia-induced ischemic retinopathy were established. Angiostatin or normal saline (NS) were injected into the vitreous in 5 groups: normal, control and various doses. The nuclei of new vessel buds extending from the retina into the vitreous in different groups were counted and compared under the light microscope. RESULTS: Angiostatin could inhibit the growth of microvascular endothelial cells from rat retina in vitro. There were plenty of new vessel buds in the eyes of all mice in hyperoxic condition. The number of the nuclei of new vesselbuds in the murine eyes with injection of angiostatin. They were reduced by 42% (P < 0.01), 57% (P < 0.01) and 82% (P < 0.01) respectively. CONCLUSION: Angiostatin can powerfully inhibit growth of microvascular endothelial cells. The proliferation of retinal vessel may be suppressed by using angiostatin.

Angiogenesis Inhibitors↗
PubMedDate not supplied

Retinal neovascularization and an angioma-like lesion after demarcation photocoagulation for rhegmatogenous retinal detachment.

Laser photocoagulation might aggravate the ischemia of an area of retinal detachment and predispose the retina to formation of neovascularization and an angioma-like lesion. We present a case of retinal neovascularization (RNV) and an angioma-like lesion occurring after demarcation photocoagulation for rhegmatogenous retinal detachment (RRD). A 20-year-old woman suffered from a retinal atrophic hole with localized shallow retinal detachment in the right eye. Laser photocoagulation was performed to wall off the area of detachment. Fifteen months later, RNV and an angioma-like lesion had developed in the previously detached retina. Treatment with demarcation photocoagulation for RRD may run a risk of formation of RNV and angioma-like lesion if the retina is not reattached.

Adult↗
PubMed2006

Vasohibin is up-regulated by VEGF in the retina and suppresses VEGF receptor 2 and retinal neovascularization.

Vasohibin is a recently identified protein that is up-regulated in cultured vascular endothelial cells by vascular endothelial growth factor and fibroblast growth factor 2. It inhibits endothelial cell migration, proliferation, and tube formation, and suppresses angiogenesis in chick chorioallantoic membrane, after subcutaneous implantation of matrigel, and in a tumor xenograft model. This has led to the hypothesis that vasohibin functions as a negative feedback inhibitor of angiogenesis. In this study, we tested that hypothesis in a well-characterized model of retinal neovascularization. In ischemic retina, increased expression of VEGF was accompanied by elevation of vasohibin mRNA and blocking of the increase in vegf mRNA with vegf siRNA significantly attenuated the rise in vasohibin mRNA. In transgenic mice in which the rhodopsin promoter drives expression of VEGF in the retina, there was also a significant increase in vasohibin mRNA. In mice with ischemic retinopathy, there was increased expression of vasohibin in vascular endothelial cells, and vasohibin knockdown caused an increase in neovascularization. Conversely, intraocular injection of recombinant vasohibin or an adenoviral vector containing a vasohibin expression cassette strongly suppressed retinal neovascularization in mice with ischemic retinopathy. Knockdown of vasohibin mRNA in ischemic retina had no significant effect on vegf or vegf receptor 1 mRNA levels but caused a significant elevation in the level of vegf receptor 2 mRNA. These data support the hypothesis that vasohibin acts as a negative feedback regulator of neovascularization in the retina and suggest that suppression of VEGF receptor 2 may play some role in mediating its activity.

Animals↗
PubMed2005

Genistein inhibited retinal neovascularization and expression of vascular endothelial growth factor and hypoxia inducible factor 1alpha in a mouse model of oxygen-induced retinopathy.

The effects of genistein on neovascularization, vascular endothelial growth factor (VEGF), and hypoxia inducible factor 1alpha (HIF1alpha) protein expression in a mouse model of oxygen-induced retinopathy were studied. The model of oxygen-induced retinal neovascularization was induced in newborn C57BL/6 mice by exposing 7-day-old mice to 75% oxygen for 5 days and then housing them in room air (relative hypoxia). Retinopathy was assessed by quantitation of vascular cell nuclei anterior to inner limiting membrane. Judged by relative fluorescence using a confocal scanning laser microscope coupled to a computer, VEGF and HIF1alpha protein expression were investigated. Genistein markedly inhibited the numbers of nuclei protruding above the inner limiting membrane under relative hypoxia conditions. The levels of nuclei numbers were suppressed by 50, 100, and 200 mg/kg body weight /day genistein to 87.4%, 72.0%, and 59.4%, respectively, compared to that untreated with genistein. VEGF protein was constitutively expressed in the preretinal area under normoxia conditions. Genistein markedly inhibited relative-hypoxia-elicited VEGF expression elevation in a dose-dependent manner. HIF1alpha expression was also observed in normoxia conditions. There was a 2.4-fold induction in preretinal HIF1alpha expression in oxygen-reared animals when compared to room-air-reared animals. Genistein dose-dependently suppressed HIF1alpha protein expression. These results indicated that the inhibition of VEGF and HIF1alpha protein expression by genistein may partly account for its effect on retinal neovascularization in vivo, and genistein could be an effective agent in the prevention and treatment of ocular neovascularization.

Angiogenesis Inhibitors↗
PubMed2007

New quantitative analysis, using high-resolution images, of oxygen-induced retinal neovascularization in mice.

Oxygen-induced retinopathy (OIR) has been widely studied as an animal model of retinal neovascularization diseases. Evaluation using this model is mainly performed by counting cell nuclei above the internal limiting membrane in serial cross-sections or by scoring in flat-mounted retinas. Quantitative evaluation is important for accurate elucidation of pathological conditions and the drug evaluations. We therefore attempted quantification using new imaging software and high-resolution images taken with a high-resolution CCD camera. Neonatal mice were exposed to 75% oxygen from postnatal day 7 (P7) to P12, then returned to room air until P17. At each evaluation time, mice were perfused with fluorescein-dextran, and flat-mounted retinas were prepared. Total images of the retinal vasculature were collected and analyzed using the imaging software. P17 normal retinas showed increases in computerized total tube area, total tube length, number of segments, and number of branch points (versus P7 normal retinas). These increases coincided with the development of the retinal vasculature between P7 and P17. P17 OIR retinas similarly showed increases in those parameters, and the number of nodes (thick regions exceeding the maximum width of the vessel) and the node area (abnormality induced by OIR) were markedly increased (versus P17 normal retinas). Accordingly, this approach is considered most suitable for evaluating the number of nodes and node area in this model. Quantification using the present imaging software should be useful for evaluating physiological and pathological neovascularizations in this OIR model.

Animals↗
PubMed1985

Peripheral retinal neovascularization in diabetes mellitus.

The cases of seven patients with diabetes mellitus and peripheral proliferative retinopathy (retinal neovascularization at or anterior to the equator) were studied. Associated abnormalities found included systemic arterial hypertension in five, a positive fluorescent treponemal antibody titer in four, and benign monoclonal gammopathy, intravenous drug abuse and hemoglobin AS each in one patient. The presence of additional systemic diseases should be suspected in diabetic patients with predominantly peripheral proliferative retinopathy.

Adult↗
PubMed2005

Treatments for choroidal and retinal neovascularization: a focus on oligonucleotide therapy and delivery for the regulation of gene function.

Blinding eye diseases caused by neovascularization of the retinal tissue are the leading cause of blindness in Western societies. Current treatments, such as laser photocoagulation, are limited in their effectiveness at halting the progression of angiogenesis and are unable to reduce the number of vessels once they have developed. In addition, although complete blindness is often avoided, vision is often permanently impaired by the treatment itself. Several less invasive treatments are being developed and one of these is oligonucleotide gene therapy in which short stretches of nucleotides are being used as inhibitors of key, metabolic processes involved in angiogenesis. Combined with this is the development of new and improved nucleotide chemistries aimed at overcoming many of the problems associated with oligonucleotide gene therapy, such as poor longevity because of endonuclease activity. In addition, advancements in delivery systems have further enhanced the efficacy of oligonucleotide gene therapy by increasing cellular penetration and localizing delivery to specific cell types and organs.

Choroidal Neovascularization↗
PubMed2006

Specific involvement of SRC family kinase activation in the pathogenesis of retinal neovascularization.

PURPOSE: Src family kinases (SFKs) are membrane-attached nonreceptor protein tyrosine kinases that link a variety of extracellular cues to intracellular signal pathways. The purpose of this study was to characterize the roles of SFKs in vascular endothelial growth factor (VEGF)-mediated retinal angiogenesis. METHODS: Primary rat retinal glial Müller cells and bovine and human retinal microvascular endothelial cells (RMECs) were used in the in vitro studies. A rat model of retinopathy of prematurity (ROP) was used in the in vivo studies. RESULTS: In vitro, SFKs were essential for hypoxia-induced VEGF expression in Müller cells and for VEGF signaling in RMECs. However, neither process required significant further phosphorylation of the SFK activation loop Tyr416. In vivo, in a rat model of ROP, a pronounced increase of retinal SFK Tyr416 phosphorylation was observed that was specifically associated with pathologic angiogenesis. These retinas also expressed significantly higher levels of VEGF than did those in healthy controls. Immunohistochemical analysis indicated that Müller cells were the major source of the elevated level of phospho-SFK Tyr416. Intravitreous injection of a selective SFK inhibitor, PP2, significantly reduced retinal VEGF and retinopathy in the ROP model, indicating that SFKs acted as important regulators in abnormal retinal angiogenesis. CONCLUSIONS: Together, these data suggest that SFK activation through a Tyr416-dependent mechanism may be an important factor in the pathogenesis of retinal neovascularization.

Animals↗