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At least 1,621 records · Page 90Linked to original sources
PubMed2004

Vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor: implications for ocular angiogenesis.

PURPOSE: Pigment epithelium-derived factor (PEDF) has been demonstrated to suppress ocular angiogenesis in several animal models. In this study, we sought to measure the levels of PEDF and vascular endothelial growth factor (VEGF) in the vitreous of patients with and without ocular neovascular disorders. DESIGN: Case-control study of patients undergoing intraocular surgery for a variety of neovascular and nonneovascular conditions. METHODS: Vitreous samples were collected from 65 eyes of 65 patients with no neovascular disorder (n = 24), choroidal neovascularization (n = 9), active proliferative diabetic retinopathy (n = 16), and inactive proliferative diabetic retinopathy (n = 16). The levels of VEGF and PEDF in these vitreous samples were determined by enzyme-linked immunosorbent assay. RESULTS: The VEGF levels were at or below the level of detectability in the reference and choroidal neovascularization groups. The VEGF levels were significantly elevated in both the active and inactive PDR groups, and significantly higher in the active PDR group as compared with the inactive PDR group. The PEDF levels, which were present at relatively high concentrations in all groups, were higher in patients with active PDR compared with the control and choroidal neovascularization groups. CONCLUSIONS: High levels of immunoreactive PEDF are present in the vitreous of individuals with or without ocular neovascularization, but PEDF levels are significantly higher in patients with active PDR compared with patients with choroidal neovascularization or nonneovascular retinal diseases. Although these results do not preclude the possibility that endogenous PEDF helps to modulate ocular neovascularization, they do not support ischemia-induced downregulation of PEDF as a mechanism for such modulation.

Adult↗
PubMed2003

Thrombospondin-1-deficient mice exhibit increased vascular density during retinal vascular development and are less sensitive to hyperoxia-mediated vessel obliteration.

Thrombospondin-1 (TSP1) is a natural inhibitor of angiogenesis. Its expression is most prominent during the late stages of vascular development and in the adult vasculature. Our previous studies have shown that TSP1 expression promotes a quiescent, differentiated phenotype of vascular endothelial cells. However, the physiological role TSP1 plays during vascular development and neovascularization requires further delineation. Here, we investigated the role of TSP1 during development of retinal vasculature and retinal neovascularization during oxygen-induced ischemic retinopathy. The retinal vascular density was increased in TSP1-deficient (TSP1-/-) mice compared with wild-type mice. This finding was mainly attributed to increased number of retinal endothelial cells in TSP1-/- mice. During oxygen-induced ischemic retinopathy, the developing retinal vasculature of TSP1-/- mice was less sensitive to vessel obliteration induced by hyperoxia but exhibited a similar level of neovascularization induced by normoxia compared with wild-type mice. This finding is consistent with the similar pattern of VEGF expression detected in wild-type and TSP1-/- mice. Furthermore, the increased expression of TSP1 during development of retinal vasculature was not affected by oxygen-induced ischemic retinopathy. In addition, the regression of ocular embryonic (hyaloid) vessels, as well as the newly formed retinal vessels during oxygen-induced ischemic retinopathy, was delayed in TSP1-/- mice. Therefore, TSP1 is a modulator of vascular homeostasis and its expression is essential for appropriate remodeling and maturation of retinal vasculature.

Animals↗
PubMed1995

Changes associated with tyrosine phosphorylation during short-term hypoxia in retinal microvascular endothelial cells in vitro.

The occlusion of capillary vessels results in low oxygen tension in adjacent tissues which triggers a signaling cascade that culminates in neovascularization. Using bovine retinal capillary endothelial cells (BRCEC), we investigated the effects of short-term hypoxia on DNA synthesis, phosphotyrosine induction, changes in the expression of basic fibroblast growth factor receptor (bFGFR), protein kinase C (PKC alpha), heat shock protein 70 (HSP70), and SH2-containing protein (SHC). The effect of protein tyrosine kinase (PTK) and phosphatase inhibitors on hypoxia-induced phosphotyrosine was also studied. Capillary endothelial cells cultured in standard normoxic (pO2 = 20%) conditions were quiesced in low serum containing medium and then exposed to low oxygen tension or hypoxia (pO2 = 3%) in humidified, 5% CO2, 37 degrees C, tissue culture chambers, on a time-course of up to 24 h. DNA synthesis was potentiated by hypoxia in a time-dependent manner. This response positively correlated with the cumulative induction of phosphotyrosine and the downregulation of bFGFR (M(r) approximately 85 kDa). Protein tyrosine kinase inhibitors, herbimycin-A, and methyl 2,5-dihydroxycinnamate, unlike genistein, markedly blocked hypoxia-induced phosphotyrosine. Prolonged exposure of cells to phosphatase inhibitor, sodium orthovanadate, also blocked hypoxia-induced phosphotyrosine. The expression of HSP70, PKC alpha, and SHC were not markedly altered by hypoxia. Taken together, these data suggest that short-term hypoxia activates endothelial cell proliferation in part via tyrosine phosphorylation of cellular proteins and changes in the expression of the FGF receptor. Thus, endothelial cell mitogenesis and neovascularization associated with low oxygen tension may be controlled by abrogating signaling pathways mediated by protein tyrosine kinase and phosphatases.

Animals↗
PubMed1991

Retinochoroidal coloboma and subretinal neovascularization.

Subretinal neovascularization associated with retinochoroidal coloboma is rare. To the authors' knowledge, only three cases have been reported. We report a new case of isolated subretinal neovascularization and coloboma in a 26-year-old woman without other causes of choroidal neovascularization. Only the disruption of the normal retinal anatomy could explain the development of this subretinal neovascularization.

Adult↗
PubMed2000

Overexpression of vascular endothelial growth factor (VEGF) in the retinal pigment epithelium leads to the development of choroidal neovascularization.

Vascular endothelial growth factor (VEGF) has been strongly implicated in the development of choroidal neovascularization found in age-related macular degeneration. Normally expressed in low levels, this study investigates whether the overexpression of VEGF in the retinal pigment epithelium is sufficient to cause choroidal neovascularization in the rat retina. A recombinant adenovirus vector expressing the rat VEGF(164) cDNA (AdCMV.VEGF) was constructed and injected into the subretinal space. The development of neovascularization was followed by fluorescein angiography, which indicates microvascular hyperpermeability of existing and/or newly forming blood vessels, and histology. VEGF mRNA was found to be overexpressed by retinal pigment epithelial cells and resulted in leaky blood vessels at 10 days postinjection, which was maintained for up to 31 days postinjection. By 80 days postinjection, new blood vessels had originated from the choriocapillaris, grown through the Bruch's membrane to the subretinal space, and disrupted the retinal pigment epithelium. This ultimately led to the formation of choroidal neovascular membranes and the death of overlying photoreceptor cells. By controlling the amount of virus delivered to the subretinal space, we were able to influence the severity and extent of the resulting choroidal neovascularization. These results show that even temporary overexpression of VEGF in retinal pigment epithelial cells is sufficient to induce choroidal neovascularization in the rat eye.

Adenoviridae↗
PubMed1989

[Indications for photocoagulation in idiopathic retinal periphlebitis].

Fourteen patients (23 eyes) with idiopathic retinal periphlebitis were followed during a mean time of six years. Argon laser photocoagulation was performed in 18 eyes: in 11 eyes for large retinal ischemic areas, and in 7 eyes for disc or peripheral neovascularization. Beneficial results were obtained in 72.5% of the treated patients. Laser photocoagulation seems to be useful to prevent or reduce ocular neovascularization associated with idiopathic retinal periphlebitis, and to prevent vitreous hemorrhage. Photocoagulation did not increase ocular inflammation and should be limited to ischemic areas.

Adult↗
PubMed2000

[Development of neovascularization of the optic papilla, retina and iris. Dependence on site and extent of retinal ischemia].

BACKGROUND: Is it possible to find a correlation between the localisation of neovascularisations and the localisation and extension of the retinal ischemia? Ischemia was recognized not as capillary non-perfusion but as impaired retinal perfusion. MATERIALS AND METHODS: Patients with retinal ischemia like in diabetic retinopathy (n = 95), central retinal vein occlusion (n = 9), ischemic ophthalmopathia (n = 8) and branch vein occlusion (n = 5) who had neovascularisations were examined. The localisation of retinal ischemia and the localisation of neovascularisations were diagnosed by fluorescein angiography and biomicroscopy. RESULTS: Neovascularisations at the different places were observed with different frequencies depending on localisation and extension of retinal ischemia. Panretinal ischemia caused by diabetic retinopathy type B was followed by neovascularisations at iris in 69.2% with participation of the anterior chamber angle in 61.1%. In diabetic retinopathy type A with limited retinal ischemia neovascularisations of iris and chamber angle were significantly less frequent (31.7%/25%). On the contrary panretinal ischemia caused by central retinal vein occlusion was followed by neovascularisations elsewhere in 11.1%; in diabetic retinopathy type C with limited retinal ischemia neovascularisations elsewhere were observed only in 66.7%. CONCLUSIONS: There is a relationship between the localisation of the neovascularisations and the localisation and the extension of the retinal ischemia. The differentiation of PDR in different ischemic types is confirmed by different frequencies of the neovascularisation sites depending on the ischemic type. The explanation for the frequent finding of neovascularisations at the disk caused by the peripheral type of diabetic retinopathy is a communication via Cloquet's canal between periperal retina and papilla.

Diabetic Retinopathy↗
PubMed2004

Somatostatin inhibits IGF-1 mediated induction of VEGF in human retinal pigment epithelial cells.

Neovascularization stimulated by IGF-1 mediated induction of vascular endothelial growth factor (VEGF) is one of the leading causes of blindness in humans. It plays a central role in the pathogenesis of proliferative diabetic retinopathy (DR), neovascular glaucoma, exudative age-related macular degeneration (AMD) and retinopathy of prematurity. Neovascularization is a multi-step process that involves complex interactions of a variety of mitogenic factors such as VEGF and IGF-I which are produced locally in the human eye by a variety of cells including retinal pigment epithelial (RPE) cells, retinal capillary pericytes, endothelial cells, Mueller cells and ganglion cells. We hypothesized that somatostatin would inhibit the IGF-1 signal transduction pathway in RPE cells, resulting in decreased VEGF production. We have observed expression of somatostatin receptor protein in retinal pigment epithelial (RPE) cells of the human eye using immunohistochemistry and have confirmed expression of somatostatin receptors in cultured human RPE cells using reverse transcriptase-PCR. IGF-1 induced a dose dependent increase in IGF-1R phosphorylation and in VEGF mRNA levels in cultured human RPE cells. Somatostatin and octreotide, a somatostatin analogue, inhibited IGF-1 receptor (IGF-1R) phosphorylation and decreased VEGF production. Both IGF-1R phosphorylation and accumulation of VEGF mRNA were inhibited by physiological levels of somatostatin and octreotide (1 nM). These results demonstrate somatostatin and octreotide mediated attenuation of both IGF-1R signal transduction and VEGF mRNA accumulation via somatostatin receptor type 2 (sst2). Furthermore, these data suggest a rationale for the use of octreotide as a prophylactic and therapeutic option in disease states that cause ocular neovascularization.

Cells, Cultured↗
PubMedDate not supplied

[Chorioretinal coloboma and neovascular membrane].

Retinochoroidal coloboma results from an incomplete closure of the ocular embryonic fissure. Uni or bilateral, the coloboma can be associated with cataract, microphthalmia, retinal detachment... but rarely with neovascularization. This association is comparable with subretinal neovascularization in high myopia, angioid streaks, choroiditis and choroidal ruptures. The disruption of the normal anatomy of the Bruch's membrane is a possible entry site of choroidal blood vessels. But the reason why only rare cases are reported is unknown.

Adult↗
PubMed2000

Inhibition of experimental choroidal neovascularization by overexpression of tissue inhibitor of metalloproteinases-3 in retinal pigment epithelium cells.

PURPOSE: To evaluate the feasibility of introducing exogenous tissue inhibitor of metalloproteinases-3 gene into the rat retinal pigment epithelium using hemagglutinating virus of Japan liposomes and to assess the effect of tissue inhibitor of metalloproteinases-3 overexpression in retinal pigment epithelium cells on the formation of experimental choroidal neovascularization. METHODS: Hemagglutinating virus of Japan liposomes containing hemagglutin epitope-tagged tissue inhibitor of metalloproteinases-3 gene were injected into the subretinal space in rat eyes. Localization of oligonucleotides was evaluated by fluorescence microscopy. Exogenous tissue inhibitor of metalloproteinases-3 mRNA expression was assessed by reverse transcribed polymerase chain reaction. Exogenous tissue inhibitor of metalloproteinases-3 protein expression was visualized by immunostaining with monoclonal antibody 12CA5 against the hemagglutin epitope. Three days after transfection of tissue inhibitor of metalloproteinases-3 gene into retinal pigment epithelium cells, intense laser photocoagulation was performed and the incidence of choroidal neovascularization was assessed by fluorescein fundus angiography. RESULTS: Exogenous tissue inhibitor of metalloproteinases-3 mRNA expression in the choroid and retina was detected on day 3. The efficiency of tissue inhibitor of metalloproteinases-3 gene transfection into retinal pigment epithelium cells was greatest on day 7 and decreased gradually thereafter. The incidence of choroidal neovascularization in tissue inhibitor of metalloproteinases-3 gene-transfected eyes was markedly decreased compared with controls. CONCLUSIONS: This study shows that tissue inhibitor of metalloproteinases-3 gene can be transferred into rat retinal pigment epithelium using the hemagglutinating virus of Japan-liposome method and that tissue inhibitor of metalloproteinases-3 gene overexpression can inhibit development of experimental choroidal neovascularization. This method may represent a future treatment modality for human macular degeneration associated with choroidal neovascularization.

Animals↗
PubMed1989

Ocular complications of arteriovenous communications of the retina.

Primary arteriovenous communications of the retina (AVCR) are usually considered to be stable retinal lesions. Complications were documented in seven cases of AVCR, including intraretinal macular hemorrhage, central and peripheral retinal vein occlusions, neovascular glaucoma, and vitreous hemorrhage. To explain these developments, a hypothesis is presented that AVCR are associated with localized decreased retinal arterial pressure, increased retinal venous pressure, increased turbulence of blood flow, and decreased perfusion of adjacent retinal tissues.

Adolescent↗
PubMed2003

Gene therapy for ocular angiogenesis.

Ocular neovascularization is a central feature of diabetic retinopathy and age-related macular degeneration. These conditions are the major causes of blindness in the developed world. Current treatments are of limited efficacy and associated with significant adverse effects. Characterization of the molecular and cellular events involved in angiogenesis has led to the identification of a number of angiostatic molecules with potential therapeutic value. The systemic administration of small molecule angiostatic proteins risks significant systemic adverse effects and the effect of their intraocular injection is short-lived. Local gene transfer, however, offers the possibility of targeted, sustained and regulatable delivery of angiostatic proteins to the retina after a single procedure to introduce a vector to an intraocular site. The effect of intra-ocular delivery of recombinant viruses carrying genes encoding angiostatic proteins has been demonstrated in rodent models of ocular neovascularization. Recombinant adeno-associated virus-mediated local gene transfer of a vascular endothelial growth factor inhibitor controls both retinal and choroidal neovascularization. The clinical application of this approach may require the means to regulate gene expression in order to minimize the potential for adverse effects. Regulation of transgene expression by means of a hypoxia-responsive promoter offers an attractive strategy for the targeted and regulated delivery of angiostatic proteins to the retina in the management of ischaemia-induced ocular neovascularization. Preclinical studies of gene transfer in a large animal model following subretinal delivery of a recombinant adeno-associated virus vector have demonstrated efficient sustained reporter gene expression in cells of the outer retina. Recent progress has enabled the planning of clinical trials of gene therapy for ocular neovascular disorders.

Aged↗
PubMedDate not supplied

Non-paralleled increase of hepatocyte growth factor and vascular endothelial growth factor in the eyes with angiogenic and nonangiogenic fibroproliferation.

Vascular endothelial growth factor (VEGF) has been known as principal angiogenic factor in vasculogenesis, tumor angiogenesis and ocular angiogenesis. Currently, hepatocyte growth factor (HGF) has been reported to play a major role in ocular angiogenesis. We studied distribution of both growth factors in angiogenic and non-angiogenic fibroproliferation to determine the correlation of VEGF and HGF in retinal angiogenesis. Concentrations of VEGF and HGF molecules in vitreous samples from 27 eyes with angiogenic proliferative diabetic retinopathy (PDR) and 9 eyes with non-angiogenic proliferative vitreoretinopathy (PVR) were measured by enzyme-linked immunosorbent assay (ELISA). Vitreous samples with idiopathic macular role (IMH) served as a control. Concentrations of VEGF in the angiogenic PDR were 4.3 +/- 5.8 ng/ml (mean +/- SD), and were significantly higher than in non-angiogenic PVR (0.5 +/- 0.1 ng/ml). No significant differences were observed on VEGF concentrations between PVR to control. On the contrary, HGF concentrations were significantly higher in PVR (22.5 +/- 21.8 ng/ml) than in control (6.9 +/- 5.2 ng/ml), those of PDR (24.0 +/- 16.3 ng/ml) were also significantly higher than control. Among PDR samples, VEGF concentration was significantly higher than in the subgroup with higher angiogenic activity represented by iris neovascularization, although there were no significant differences on HGF concentration between the subgroups. Focal increases in HGF on fibroproliferation in the eye regardless of the involvement of angiogenesis were not in remarkable relation with angiogenic activity, unlike VEGF. These data suggested a more extensive role of HGF than VEGF strictly related to angiogenesis.

Diabetic Retinopathy↗
PubMed1996

Histological evaluation of the canine retinal vasculature following chronic systemic administration of basic fibroblast growth factor.

The purpose of the present study was to determine if prolonged systemic arterial administration of basic fibroblast growth factor (bFGF) at a dose sufficient to enhance collateral vessel formation in the ischaemic hearts of dogs would produce retinal neovascularisation in these same animals. Adult dogs (15-25 kg) were subjected to gradual occlusion of a coronary artery and randomised to receive 1 of 3 treatments via an indwelling left atrial catheter: (1) bFGF 1.74 mg/d, 5 d/wk for 63 d (n = 7); (2) bFGF 1.74 mg/d, 5 d/wk, for 35 d followed by physiological saline, 5 d/wk, for 28 d (n = 10); or (3) physiological saline, 5 d/wk, for 63 d (n = 10). After 63 d the retinal vasculatures from these dogs were isolated and examined for capillary varicosity, neovascularisation and other histopathological signs of angiopathy. All data were collected under masked conditions. The results suggest that chronic, systemic arterial administration of bFGF stimulates neovascularisation in the ischemic myocardium, but has no significant structural or vasoproliferative effect on the nonischaemic retina of the same animal.

Animals↗
PubMed1999

Idiopathic polypoidal choroidal vasculopathy in Japanese patients.

OBJECTIVE: To describe the vascular nature and clinical features of idiopathic polypoidal choroidal vasculopathy in Japanese patients. METHODS: Patients thought to have idiopathic polypoidal choroidal vasculopathy were examined with binocular ophthalmoscopy, slitlamp biomicroscopy with a contact lens, fluorescein angiography, and indocyanine green angiography. RESULTS: From January 1993 to December 1997, 35 eyes in 32 patients were diagnosed as having idiopathic polypoidal choroidal vasculopathy. Men were predominantly affected (22 patients [69%]). Most patients were unilaterally involved (29 patients [91%]) and elderly, with a mean age of 65.7 years (range, 44-82 years). Ocular manifestations were relatively mild, with serous or hemorrhagic detachments of the retinal pigment epithelium and neurosensory retina in the posterior pole. Most patients had a favorable course, although some experienced recurrence, and a few eyes developed disciform scarring. In all patients, indocyanine green angiograms demonstrated branching vascular networks with polypoidal dilations at terminals of the network beneath the retinal pigment epithelium. These lesions were mostly in the macula (33 eyes [94%]), with a few in the peripapillary area. CONCLUSIONS: Idiopathic polypoidal choroidal vasculopathy in Japanese patients differs from that in American patients. It seems that this disorder occurs in elderly Japanese patients and should be treated as a distinct clinical entity. It is probably a peculiar form of choroidal neovascularization beneath the retinal pigment epithelium. We propose the term "polypoidal choroidal neovascularization" for this disorder.

Adult↗
PubMed2005

[Viral and nonviral gene therapy for treatment of retinal diseases].

The development of gene therapeutic approaches offers new perspectives for the treatment of retinal diseases. The use of both, nonviral methods employing oligonucleotides as well as viral expression vectors provide the possibility to treat neovascularization defects and retinal degeneration, respectively. The mechanism by which the therapeutic oligonucleotides (antisense oligonucleotides, aptamers and siRNA) work is based on degradation of specific transcripts. Consequently, a reduction of the corresponding protein, which is involved in the particular pathogenesis, follows. In contrast, viral vector transduction can substitute the disease-associated gene with an intact copy. So far, animal models have successfully contributed to the development of gene therapeutic medication and further treatments are at the recruiting phase of clinical trials.

Animals↗
PubMed1988

Acute multifocal hemorrhagic retinal vasculitis.

The authors present a series of seven patients with acute visual loss associated with mild anterior uveitis, multifocal retinal vasculitis, retinal capillary nonperfusion, retinal hemorrhage, disc swelling, and vitreitis. Oral prednisone was of some benefit in these patients and oral acyclovir was generally ineffective. Neovascular complications including retinal, disc, choroidal, and iris new vessels were common, requiring photocoagulation in five patients. Horseshoe tears developed in two patients in zones of uninvolved retina but retinal detachment did not occur. The etiology remains unknown, although it may represent either a localized ocular form of Behçet's disease or other systemic syndrome, infection with a herpes group virus other than zoster varicella virus, or a manifestation of an undefined infectious agent.

Acute Disease↗
PubMed1984

Proliferative lupus retinopathy.

Preretinal neovascularization in response to retinal vascular occlusions developed in two patients receiving treatment for systemic lupus erythematosus. In both patients, the preretinal neovascularization was asymptomatic and was discovered on routine ocular examination. One patient required bilateral peripheral ablative argon-laser therapy for florid preretinal neovascularization. This patient had severe occlusive retinal vasculitis despite serologic evidence of remission of the underlying disease process.

Adolescent↗