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Results for “Retinal Neovascularization”

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At least 19 recordsLinked to original sources

PubMed1997

Essential role of growth hormone in ischemia-induced retinal neovascularization.

Retinal neovascularization is the major cause of untreatable blindness. The role of growth hormone (GH) in ischemia-associated retinal neovascularization was studied in transgenic mice expressing a GH antagonist gene and in normal mice given an inhibitor of GH secretion (MK678). Retinal neovascularization was inhibited in these mice in inverse proportion to serum levels of GH and a downstream effector, insulin-like growth factor-I (IGF-I). Inhibition was reversed with exogenous IGF-I administration. GH inhibition did not diminish hypoxia-stimulated retinal vascular endothelial growth factor (VEGF) or VEGF receptor expression. These data suggest that systemic inhibition of GH or IGF-I, or both, may have therapeutic potential in preventing some forms of retinopathy.

Animals↗

PubMed1996

Subcutaneous injection of a cyclic peptide antagonist of vitronectin receptor-type integrins inhibits retinal neovascularization.

Retinal neovascularization is a major cause of blindness in such disorders as retinopathy of prematurity, proliferative diabetic retinopathy and senile macular degeneration. Because ligation of vitronectin receptor-type integrins appears to be required for the survival and maturation of newly formed but not quiescent blood vessels in several vascular beds including the retina, blockade of this downstream adhesion receptor system was investigated. In a mouse model of hypoxia-induced retinal neovascularization twice daily administration of 1 to 20 mg cyclic alpha v-integrin antagonist peptide per kilogram of body weight reduced capillary proliferation in a dose-dependent fashion--maximum 76%--without obvious side effects. A cyclic control peptide displayed no inhibitory effect on neovascularization. These findings indicate that systemic application of vitronectin receptor antagonists appears to be clinically feasible and is efficient in preventing retinal neovascularization and superior to cytokine-blocking strategies.

Amino Acid Sequence↗

PubMed2001

Unbalanced expression of VEGF and PEDF in ischemia-induced retinal neovascularization.

Retinal levels of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF), an angiogenic inhibitor, were measured and correlated with the ischemia-induced retinal neovascularization in rats. The retinas with neovascularization showed a 5-fold increase in VEGF while 2-fold decrease in PEDF, compared to the age-matched controls, resulting in an increased VEGF/PEDF ratio. The time course of the VEGF/PEDF ratio change correlated with the progression of retinal neovascularization. Changes in the VEGF and PEDF mRNAs preceded their protein level changes. These results suggest that an unbalance between angiogenic stimulators and inhibitors may contribute to retinal neovascularization.

Animals↗

PubMed1981

Arrest and regression of retinal neovascularization.

Retinal neovascularization is one of many forms of new vessel formation in the eye. The chief cause is diabetic retinopathy and the severe retinal and vitreous complications can now be significantly reduced by argon laser and xenon arc coagulation. Although the natural history of proliferative retinopathy is well described, clinical details of monitoring the progress and regression have not been described. This paper describes the signs of active proliferation of arrest and regression both spontaneously and as a result of laser photocoagulation. Vitreous detachment is considered in some detail together with the factors which control the visual outcome after this significant event in the natural history of the retinopathy. The purpose of the paper is to provide a more rational approach to photocoagulation of retinal neovascularization.

Diabetic Retinopathy↗

PubMed2002

Characterization of protein kinase C beta isoform's action on retinoblastoma protein phosphorylation, vascular endothelial growth factor-induced endothelial cell proliferation, and retinal neovascularization.

Retinal neovascularization is a major cause of blindness and requires the activities of several signaling pathways and multiple cytokines. Activation of protein kinase C (PKC) enhances the angiogenic process and is involved in the signaling of vascular endothelial growth factor (VEGF). We have demonstrated a dramatic increase in the angiogenic response to oxygen-induced retinal ischemia in transgenic mice overexpressing PKC beta 2 isoform and a significant decrease in retinal neovascularization in PKC beta isoform null mice. The mitogenic action of VEGF, a potent hypoxia-induced angiogenic factor, was increased by 2-fold in retinal endothelial cells by the overexpression of PKC beta 1 or beta 2 isoforms and inhibited significantly by the overexpression of a dominant-negative PKC beta 2 isoform but not by the expression of PKC alpha, delta, and zeta isoforms. Association of PKC beta 2 isoform with retinoblastoma protein was discovered in retinal endothelial cells, and PKC beta 2 isoform increased retinoblastoma phosphorylation under basal and VEGF-stimulated conditions. The potential functional consequences of PKC beta-induced retinoblastoma phosphorylation could include enhanced E2 promoter binding factor transcriptional activity and increased VEGF-induced endothelial cell proliferation.

Animals↗

PubMed2002

Differential effects of bactericidal/permeability-increasing protein (BPI) analogues on retinal neovascularization and retinal pericyte growth.

PURPOSE: Bactericidal/permeability-increasing protein (BPI), an antibacterial and lipopolysaccharide-neutralizing protein, also has an antiangiogenic effect. To evaluate the therapeutic role of BPI in ischemic retinopathies, the antiangiogenic activity of a human recombinant 21-kDa modified N-terminal fragment of BPI (rBPI(21)), which has the biological properties of the holoprotein, and a peptidomimetic (XMP.Z) derived from BPI were examined. METHODS: The effects of rBPI(21) and XMP.Z on VEGF-induced growth of bovine retinal microvascular endothelial cells (BRECs) and on serum-induced growth of bovine retinal pericytes (BRPs) and retinal pigment epithelial cells (BRPECs) were evaluated by determining total DNA content. The neonatal mouse model of retinopathy of prematurity (ROP) was used to study the effect of XMP.Z in vivo. Intraperitoneal injections of the peptidomimetic (10 mg/kg) were administered every 24 hours for 5 days (postnatal [P]12-P17) during induction of neovascularization. Retinal neovascularization was evaluated using flatmounts of fluorescein-dextran-perfused retinas and quantitated by counting retinal cell nuclei anterior to the internal limiting membrane. RESULTS. VEGF (25 ng/mL) increased the total DNA per well of BRECs by 120% +/- 50% (P < 0.001), which was inhibited by addition of rBPI(21) or XMP.Z, with decreases of 77% +/- 15% (P < 0.05) and 107% +/- 19% (P < 0.01) at maximum effective doses of 75 and 15 microg/mL rBPI(21) and XMP.Z, respectively. In contrast, rBPI(21) at 75 microg/mL enhanced the total DNA per well of BRP 53% +/- 14% (P < 0.001) in the presence of 5% fetal bovine serum (FBS), whereas XMP.Z enhanced BRP growth by 27% +/- 7% (P < 0.001) at 5 microg/mL. In the presence of 10% FBS, rBPI(21) and XMP.Z increased BRP growth by 91% +/- 35% (P < 0.001) and 43% +/- 18% (P < 0.01), respectively. In the oxygen-induced ROP neonatal mouse model, retinal neovascularization was decreased by 40% +/- 16% (n = 5, P < 0.01) when animals were treated with XMP.Z. CONCLUSIONS: Two BPI-derived compounds, rBPI(21) and XMP.Z, significantly suppressed VEGF-induced BREC growth in vitro, while conversely enhancing the growth of BRPs, even above that induced by 20% FBS. When tested in animals, XMP.Z also suppressed ischemia-induced retinal neovascularization in mice. These data suggest that BPI-derived compounds may have unique therapeutic potential for proliferative retinal diseases such as diabetic retinopathy, if physiological levels can be achieved in clinical settings.

Animals↗

PubMed2005

Downregulation of vascular endothelial growth factor and integrinbeta3 by endostatin in a mouse model of retinal neovascularization.

Retinal neovascularization is among the leading causes of vision impairment throughout the world. Intraocular expression of vascular endothelial growth factor (VEGF), an angiogenic protein, and integrins, a group of cell adhesion molecules, is closely correlated with neovascularization in such neovascular diseases. The purpose of this study is to determine the effect of endostatin, a potent anti-angiogenic factor, on gene expression of vascular endothelial growth factor (VEGF) and integrinbeta3 in a mouse model of oxygen-induced retinopathy. C57BL/6 mice were given intravitreous injections of 1.0 microg endostatin at P12. At P17, retinal VEGF and integrinbeta3 mRNA levels were measured by real-time quantitative PCR in the hyperoxia mice and in the endostatin-treated mice. Analysis of 12 separate experiments revealed a 3.5-fold decrease in VEGF levels between hyperoxia mice and endostatin-treated mice (p<0.01) and a 2.5-fold decrease in integrinbeta3 levels between hyperoxia mice and endostatin-treated mice (p<0.01). These data suggest that intraocular expression of VEGF and integrinbeta3 mRNA is down-regulated by endostatin, which may provide a new therapeutic approach for ocular neovascularization.

Angiogenesis Inhibitors↗

PubMed1989

Diabetes as a risk factor for retinal neovascularization in retinal vein occlusion.

We evaluated a series of patients with retinal vein occlusive disease to determine whether diabetic patients with vein occlusions developed retinal neovascularization more frequently than did nondiabetics. Retinal neovascularization occurred in 68.8% of diabetics after central retinal vein occlusion compared with 27.8% of nondiabetics. Diabetics with branch retinal vein occlusions showed no greater likelihood for subsequent retinal neovascularization than did nondiabetics.

Diabetic Retinopathy↗

PubMed1997

Peripheral retinal neovascularization and retinal vascular occlusion associated with activated protein C resistance.

PURPOSE: To describe a patient with peripheral retinal neovascularization and vascular occlusion associated with activated protein C resistance. METHODS: Case report. A 63-year-old woman was examined for acute loss of vision in both eyes. She was noted to have macular edema in both eyes as well as a macular branch vein occlusion in the right eye and a central retinal vein occlusion in the left eye. Peripheral retinal neovascularization was present in both eyes. RESULT: Extensive systemic evaluation disclosed a heterozygous state for the factor V Leiden indicating activated protein C resistance. CONCLUSION: Activated protein C resistance may be associated with peripheral retinal neovascularization.

Enzyme Activation↗

PubMed1983

Retinal neovascularization after retinal vaso-obliteration. Frequency--origin--morphology.

Retinal neovascularization (NV) was found microscopically in 76% of 74 eyes with neovascular glaucoma after retinal vaso-obliteration, and in 75% or more of eyes with any type of retinal vascular occlusive disease. Preretinal NV was encountered in 47% and prepapillary NV in 49%. Retinal arterial occlusive disease was more often an underlying condition (81%) than retinal venous occlusive disease (49%). Morphological stages of retinal NV in adults are (1) insudation and/or transudation of vessel walls (100%) with endothelial proliferation (97%) and (2) capillary formation (76%). The latter takes place via intramural capillaries (31%) and endothelial plexuses (24%), and from pre-existent capillaries. New capillaries arise from arterioles, venules and capillaries. Hyalinization can be found in any retinal vessel type. Retinal NV is primarily induced by retinal hypoxia.

Glaucoma↗

PubMed1990

[Moschcowitz syndrome and retinal neovascularization with retinal detachment].

The authors examined a patient with thrombotic thrombocytopenic purpura (Moschcowitz's disease). Six months after the patient was first seen with massive bilateral vascular occlusion, she presented with advanced retinal neovascularization in both eyes and traction retinal detachment in the left eye. While traction retinal detachment is a very rare sequela of this hematologic disorder, patients with Moschocowitz's disease should be carefully examined for early signs of ocular neovascularization in order to prevent loss of residual vision.

Adult↗

PubMed2000

Blockade of vascular endothelial cell growth factor receptor signaling is sufficient to completely prevent retinal neovascularization.

Retinal vasculogenesis and ischemic retinopathies provide good model systems for study of vascular development and neovascularization (NV), respectively. Vascular endothelial cell growth factor (VEGF) has been implicated in the pathogenesis of retinal vasculogenesis and in the development of retinal NV in ischemic retinopathies. However, insulin-like growth factor-I and possibly other growth factors also participate in the development of retinal NV and intraocular injections of VEGF antagonists only partially inhibit retinal NV. One possible conclusion from these studies is that it is necessary to block other growth factors in addition to VEGF to achieve complete inhibition of retinal NV. We recently demonstrated that a partially selective kinase inhibitor, PKC412, that blocks phosphorylation by VEGF and platelet-derived growth factor (PDGF) receptors and several isoforms of protein kinase C (PKC), completely inhibits retinal NV. In this study, we have used three additional selective kinase inhibitors with different selectivity profiles to explore the signaling pathways involved in retinal NV. PTK787, a drug that blocks phosphorylation by VEGF and PDGF receptors, but not PKC, completely inhibited retinal NV in murine oxygen-induced ischemic retinopathy and partially inhibited retinal vascularization during development. CGP 57148 and CGP 53716, two drugs that block phosphorylation by PDGF receptors, but not VEGF receptors, had no significant effect on retinal NV. These data and our previously published study suggest that regardless of contributions by other growth factors, VEGF signaling plays a critical role in the pathogenesis of retinal NV. Inhibition of VEGF receptor kinase activity completely blocks retinal NV and is an excellent target for treatment of proliferative diabetic retinopathy and other ischemic retinopathies.

Aging↗

PubMed1979

Infrequency of retinal neovascularization following central retinal vein occlusion.

Forty-eight patients with the clinical diagnosis of central retinal vein occlusion and ten surgically enulceated eyes with central retinal vein occlusion documented by histopathologic examination were studied and reviewed. Retinal neovascularization developed in only one of the ten eyes. Rubeosis iridis occurred in 14% (7) of the clinical cases and in all of the histopathologic cases. Ten eyes with neovascular glaucoma, enucleated following central retinal vein occlusion, showed absence of retinal endothelial cells. The absence of retinal capillary endothelial cells is significant in explaining the rare occurrence of retinal neovascularization following central retinal vein occlusion. However, the small number of cases may reflect a biased result. Further studies of more cases over a longer period are required to reach the final conclusion.

Humans↗

PubMed1979

Infrequency of retinal neovascularization following central retinal vein occlusion attributed to endothelial death.

48 patients with central retinal vein occlusion by clinical diagnosis and 10 eyes by histopathological documentation were studied and reviewed. Only 1 eye developed retinal neovascularization. Rubeosis iridis occurs in 14% of clinical cases and all of histopathologic cases. 10 long-standing neovascular glaucoma enucleated eyes following central retinal vein occlusion show absence of retinal endothelial cells. The absence of retinal capillary endothelial cells seems to be significant in explaining the rare occurrence of retinal neovascularization following central retinal vein occlusion. However, the small number sampling may reflect a biased result. Further prospective studies with more cases and time observation are required to draw the final conclusion.

Capillaries↗

PubMed1987

Retinal neovascularization after branch retinal arterial obstruction.

We examined two eyes from two noninsulin-dependent diabetic patients that developed vitreous hemorrhage secondary to retinal neovascularization after branch retinal arterial obstruction. Although there was no ophthalmoscopic evidence of diabetic retinopathy, diabetes mellitus may have predisposed the retinas to a neovascular response, which was precipitated by the arterial obstruction.

Adult↗

PubMed2003

Role of MCP-1 and MIP-1alpha in retinal neovascularization during postischemic inflammation in a mouse model of retinal neovascularization.

Macrophages are important participants in neovascularization. This study was designed to examine the role of the monocyte/macrophage chemotactic proteins, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1alpha (MIP-1alpha) in a mouse model of oxygen-induced ischemic retinopathy and to determine whether the morphology and distribution of macrophages/microglia are concomitantly altered. The MCP-1, MIP-1alpha mRNA levels increased at 3 h after ischemia. MCP-1, MIP-1alpha, and vascular endothelial growth factor protein levels were also increased markedly and were maximal on days 1, 0.5, and 1, respectively, after ischemia. In situ hybridization showed that MCP-1 and MIP-1alpha were localized in the hypoxic inner retina. Immunostaining demonstrated that the macrophages/microglia in the retina had morphological changes with enlarged processes, and some were closely associated with neovascular tufts at postnatal day 17. Coadministration of the neutralizing antibodies against MCP-1 and MIP-1alpha inhibited retinal neovascularization by 30%. Our data suggest that MCP-1 and MIP-1alpha are involved in the induction of retinal neovascularization and play a role in the inflammation induced by the ischemic retinopathy, possibly by modulating or attracting macrophages/microglia.

Animals↗

PubMed2006

EphrinA1 inhibits vascular endothelial growth factor-induced intracellular signaling and suppresses retinal neovascularization and blood-retinal barrier breakdown.

The Eph receptor/ephrin system is a recently discovered regulator of vascular development during embryogenesis. Activation of EphA2, one of the Eph receptors, reportedly suppresses cell proliferation and adhesion in a wide range of cell types, including vascular endothelial cells. Vascular endothelial growth factor (VEGF) plays a primary role in both pathological angiogenesis and abnormal vascular leakage in diabetic retinopathy. In the study described herein, we demonstrated that EphA2 stimulation by ephrinA1 in cultured bovine retinal endothelial cells inhibits VEGF-induced VEGFR2 receptor phosphorylation and its downstream signaling cascades, including PKC (protein kinase C)-ERK (extracellular signal-regulated kinase) 1/2 and Akt. This inhibition resulted in the reduction of VEGF-induced angiogenic cell activity, including migration, tube formation, and cellular proliferation. These inhibitory effects were further confirmed in animal models. Intraocular injection of ephrinA1 suppressed ischemic retinal neovascularization in a dose-dependent manner in a mouse model. At a dose of 125 ng/eye, the inhibition was 36.0 +/- 14.9% (P < 0.001). EphrinA1 also inhibited VEGF-induced retinal vascular permeability in a rat model by 46.0 +/- 10.0% (P < 0.05). These findings suggest a novel therapeutic potential for EphA2/ephrinA1 in the treatment of neovascularization and vasopermeability abnormalities in diabetic retinopathy.

Animals↗

PubMed1996

Retinal vascular nonperfusion and retinal neovascularization as a consequence of cytomegalovirus retinitis and cryptococcal choroiditis.

BACKGROUND: Cytomegalovirus retinitis and cryptococcal choroiditis are opportunistic infections in patients with acquired immune deficiency syndrome. These infections are associated with a retinal vasculitis and vascular attenuation. METHODS: We present a case of retinal vascular nonperfusion and retinal neovascularization in a patient with acquired immune deficiency syndrome. RESULTS: Retinal vascular nonperfusion and retinal neovascularization were confirmed by fluorescein angiography. CONCLUSIONS: This is the first reported case of retinal neovascularization in a patient with acquired immune deficiency syndrome, ocular cytomegalovirus retinitis, and cryptococcal infection.

AIDS-Related Opportunistic Infections↗