Retinal neovascularization complicating rhegmatogenous retinal detachment of long duration.
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Adult↗
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Results for “Retinal Neovascularization”
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Platelet-induced retinal neovascularization in leukemia.
Retinal changes resembling those of background diabetic or hypertensive retinopathy commonly occur in leukemia, whereas retinal neovascularization is rare. When neovascularization does occur, it is usually the result of hyperviscosity caused by a greatly increased number of circulating leukocytes. A 42-year-old woman with diabetes mellitus developed chronic myelocytic leukemia and peripheral retinal neovascularization. The hyperviscosity leading to the neovascularization was probably caused by an increased number of circulating platelets.
Adult↗
Local injection of receptor tyrosine kinase inhibitor MAE 87 reduces retinal neovascularization in mice.
PURPOSE: Retinal neovascularization occurs under the influence of angiogenic factors like vascular endothelial growth factor (VEGF). VEGF signaling is enhanced by insulin-like growth factor-1 (IGF-1). In vitro, the oxoindolinone MAE 87 inhibits angiogenic signal transduction by blocking tyrosine kinase receptors including VEGF receptor 2 (VEGFR-2), IGF-1R, fibroblast GF-1R and epidermal GFR. We investigated the effect of MAE 87 in vivo using the mouse model for oxygen induced retinopathy. METHODS: From postnatal day seven (P7) on, C57BL/6J mice were kept in a 75% oxygen environment for five days. On postnatal day 12 (P12) they received an intravitreal injection of MAE 87 in one eye and control substance in the fellow eye. The animals were sacrificed by intracardial perfusion with fluorescein-dextran solution on P17. Retinal whole mounts were prepared and ischemic retinopathy was evaluated in 26 animals using a standardized retinopathy score. RESULTS: After a single intravitreal injection of MAE 87 there were significantly less angioproliferative changes (blood vessel tufts, extra-retinal neovascularization, and blood vessel tortuosity) than in the fellow eye (p=0.007). The median retinopathy score (maximal 13) for the MAE 87 treated eyes was 6 (25th percentile: 5; 75th percentile: 7) and 8 for the control eyes (25th percentile: 5; 75th percentile: 10). CONCLUSIONS: The tyrosine kinase inhibitor MAE 87 may be a promising substance for local treatment of retinal neovascularization. Due to its ability to inhibit not only the VEGF but also the IGF-1 cascade, MAE 87 may prove especially valuable for the treatment of diabetic retinopathy.
Animals↗
Angiopoietin/Tek interactions regulate mmp-9 expression and retinal neovascularization.
The objective of the study was to determine the role of the angiopoietins in the regulation of gelatinase expression during angiogenesis, and whether inhibition of the angiopoietin/Tek interaction in vivo can suppress the extent of retinal neovascularization. Retinal microvascular endothelial cells were treated with angiopoietins and examined for the production of gelatinases. The effects of inhibiting angiopoietin binding to the Tie-2 receptor was studied in newborn mice with experimentally induced retinal neovascularization. Animals were treated with an ip injection of the Tie-2 antagonist, muTek delta Fc, while oxygen-exposed mice treated with similar concentrations of murine IgG were used as controls. The effect of muTek delta Fc on the gelatinase expression in the retina was examined by real-time RT-PCR analysis. The stimulation of cultured retinal endothelial cells with Ang-1 and -2 resulted in the increased expression of matrix metalloproteinase (MMP)-9. Ang-2 expression was up-regulated in experimental animals during the period of angiogenesis and was the greatest on Day 17 (the time of maximal angiogenic response). Histologic analysis of mice treated with the Tie-2 antagonist, muTek delta Fc, showed significant (87%; p = 0.001) inhibition of retinal neovascularization, and the response was dose-dependent. In vitro binding data support the fact that both Ang-1 and Ang-2 bind with high avidity to muTek delta Fc. The RT-PCR analysis of the retinas of the Tek-treated animals showed a similar (80%; p = 0.001) inhibition of the MMP-9 expression, which correlated with the decrease in angiogenesis. The up-regulation of gelatinases in microvascular endothelial cells by Ang-2 may be an important early response during the development of retinal neovascularization. Inhibition of the binding activity of the angiopoietins in vivo suppressed retinal neovascularization concomitant with a reduction in the expression of MMP-9.
Angiogenesis Inducing Agents↗
Leptin stimulates ischemia-induced retinal neovascularization: possible role of vascular endothelial growth factor expressed in retinal endothelial cells.
Diabetic retinopathy is the leading cause of new blindness in adults in developed countries. Leptin, an adipocyte-derived hormone, stimulates endothelial proliferation and angiogenesis. This study was designed to elucidate the pathophysiologic role of leptin in the progression of retinal neovascularization. Using the retinopathy of prematurity model, a mouse model of ischemia-induced retinal neovascularization, we have demonstrated more pronounced retinal neovascularization in 17-day-old transgenic mice overexpressing leptin than in age-matched wild-type littermates. Ischemia-induced retinal neovascularization was markedly suppressed in 17-day-old leptin-deficient ob/ob mice. Western blot analysis revealed that a biologically active leptin receptor isoform is expressed in mouse retinal endothelial cells. Leptin receptor expression was also detected in primary cultures of porcine retinal endothelial cells, where it upregulated vascular endothelial growth factor (VEGF) mRNA expression. This effect was thought to be mediated at least partly through the activation of signal transducers and activators of transcription (STAT)3, because adenoviral transfection of the dominant-negative form of STAT3 abolished the leptin-induced upregulation of VEGF mRNA expression in retinal endothelial cells. This study provides evidence that leptin stimulates the ischemia-induced retinal neovasucularization possibly through the upregulation of endothelial VEGF, thereby suggesting that leptin antagonism may offer a novel therapeutic strategy to prevent or treat diabetic retinopathy.
Animals↗
Retinitis pigmentosa and retinal neovascularization.
Four patients with retinitis pigmentosa and either disc or peripheral retinal neovascularization with recurrent vitreous hemorrhage are described. One patient with peripheral retinal neovascularization also had rubeosis and neovascular glaucoma. The effects of relative hyperoxia on the retinal microcirculation in retinitis pigmentosa as well as intraocular inflammation may account for such changes. Laser photocoagulation appears effective in preventing vitreous hemorrhage in these patients, but systemic administration of corticosteroids did not cause the new vessels to regress.
Adult↗
Suppressed expression of tubedown-1 in retinal neovascularization of proliferative diabetic retinopathy.
PURPOSE: Retinal neovascularization occurring as a complication of diabetes mellitus can cause vision loss and blindness. The identification and study of novel genes involved in retinal angiogenesis may define new targets to suppress retinal neovascularization in diabetes and other ocular diseases. A novel acetyltransferase subunit, tubedown-1 (tbdn-1), has been isolated, the expression of which is regulated during blood vessel development. Tbdn-1 is not detected in most adult vascular beds but persists at high levels in the adult ocular vasculature. The purpose of this study was to gain insight into the possible role of tbdn-1 in retinal blood vessels by characterizing its expression patterns in adult homeostasis and in retinal neovascularization associated with diabetes. METHODS: Western blot analysis and immunohistochemistry were performed to study the expression patterns of tbdn-1 during adult homeostasis in normal human retinas, in a model of choroid-retina endothelial capillary outgrowth in vitro, and in retinas showing neovascularization in patients with proliferative diabetic retinopathy (PDR). RESULTS: In adults during homeostasis, tbdn-1 was expressed highly in normal endothelium of retinal and limbic blood vessels. Tbdn-1 was also expressed in RF/6A, a rhesus macaque choroid-retina-derived endothelial cell line. In an in vitro model system using the RF/6A cell line, tbdn-1 expression was downregulated during the outgrowth of these cells into capillary-like structures on a reconstituted basement membrane matrix. Similar to this in vitro model, tbdn-1 expression is specifically suppressed in the endothelial cells of blood vessels and capillary fronds in vivo in both the neural retinal tissue and in preretinal membranes in eyes of patients with PDR. CONCLUSIONS: High levels of expression of tbdn-1 are associated with ocular endothelial homeostasis in adults. Conversely, low levels of tbdn-1 expression are associated with endothelial capillary outgrowth in vitro and retinal neovascularization in vivo. Because the tbdn-1 acetyltransferase subunit is a member of a family of regulatory enzymes that are known to control a range of processes, including cell growth and differentiation, through posttranslational modification, the current results support a hypothesis that tbdn-1 may be involved in maintaining homeostasis and preventing retinal neovascularization.
Acetyltransferases↗
Retinal neovascularization and ocular toxoplasmosis.
Retinal neovascularization, a rare complication of ocular toxoplasmosis, is a source of vitreous hemorrhage. We examined three patients (all women, 70, 36, and 19 years old) with inactive toxoplasmosis scars associated with occlusion of a retinal arteriole or venule passing through the scar, capillary nonperfusion, and adjacent retinal neovascularization. In two patients photocoagulation of the ischemic areas produced a cessation of hemorrhage and the disappearance of neovascularization. In the third case, the neovascular frond was avulsed from its supplying retinal arteriole without treatment.
Adult↗
Retinal neovascularization in choroidal melanoma without retinal ischemia.
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Adolescent↗
Retinal neovascularization in a case of macular branch retinal vein occlusion.
BACKGROUND: Retinal neovascularization (RNV) has never been described in cases of macular branch retinal vein occlusion (MBRVO), due to the limited amount of ischemia in this form of retinal vein occlusion. Ischemic areas as wide as 5-10 disc diameters were required by previous studies to count as ischemic cases of central or major branch retinal vein occlusion. CASE REPORT: A 56-year-old woman who had been suffering from MBRVO for 3 years presented at the posterior pole a zone of non-perfusion, extending over 7.5 disc areas, and three small tufts of RNV. RNV regressed after two subsequent laser treatments of the ischemia. Retrohyaloid hemorrhage was observed 2 months after the first treatment. CONCLUSION: Since the average diameter of the non-perfused area was about 2.75 disc diameters, this case demonstrates that small RNVs can appear in less extensive areas of ischemia than is generally believed.
Female↗
[Role of the vitreous in retinal neovascularization evaluated by a comparison of central retinal vein occlusion and branch retinal vein occlusion].
Thirty three patients (33 eyes) with central retinal vein occlusion (CRVO) and 80 patients (81 eyes) with branch retinal vein occlusion (BRVO) were studied in an attempt to investigate the role of the vitreous in the formation of retinal neovascularization. All these eyes had some areas of capillary nonperfusion confirmed by fluorescein angiography and no scatter photocoagulation before the first examination. The incidence of new vessels at the optic disc (NVD) in CRVO was not significantly different from that in BRVO. However, the incidence of new vessels elsewhere (NVE) in CRVO was significantly less than that in BRVO. Follow-up vitreous examination of 36 cases while they had not developed NVD and/or NVE showed a higher incidence of posterior vitreous detachment from the mid-peripheral retina (MP-PVD) in CRVO than in BRVO. On the other hand, there was no statistically significant difference in the incidence of posterior vitreous detachment from the optic disk (D-PVD) between CRVO and BRVO. The high incidence of MP-PVD in CRVO may explain the low incidence of NVE in CRVO.
Adult↗
Retinal neovascularization associated with acute retinal necrosis.
Unilateral acute retinal necrosis (ARN), developed in a previously healthy 17-year-old boy. Neovascularization of the retina and optic disc was observed when the opaque vitreous was removed by pars plana vitrectomy. Following surgery there was a rapid resolution of neovascularization suggesting that intraocular inflammation, rather than retinal ischemia, was the cause of new vessel formation. Analysis of vitreous mononuclear cells with monoclonal antibodies and the fluorescence-activated cell sorter (FACS) revealed mostly T cells; a pattern consistent with intraocular infection as the cause of ARN. The pathogenesis of intraocular infection is complex and some patients with ARN may be helped by systemic immunosuppression (ie, corticosteroids).
Acute Disease↗
Retinal neovascularization secondary to cytomegalovirus retinitis in Wegener's granulomatosis.
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Cytomegalovirus Infections↗
Indentation laser photocoagulation of peripheral retinal neovascularization.
The treatment of peripheral retinal neovascularization by laser photocoagulation is an accepted technique. One of its limitations is the difficulty in photocoagulating retinal neovascularization that has become even slightly elevated from the underlying pigment epithelium. The failure to close the neovascular frond and the production of a vitreous hemorrhage are the complications from the direct photocoagulation of elevated neovascularization. The currently accepted method of treating the feeding retinal arteriole and venule, although successful, requires multiple treatment sessions. The use of a scleral indentation funnel at the time of laser photocoagulation permits the direct photocoagulation of elevated neovascularization in some cases. This technique increases the number of neovascular fronds that are amenable to direct laser photocoagulation, improves the rate of success of closure of the neovascularization by photocoagulation, decreases the necessary number of treatment sessions, and decreases the risks from treatment.
Fluorescein Angiography↗
Diltiazem reduces retinal neovascularization in a mouse model of oxygen induced retinopathy.
PURPOSE: To assess the effect of diltiazem, a calcium channel blocking agent, on oxygen induced retinopathy (OIR) in a mouse model using neovascular nuclei quantitation and a quantitative scoring system based on examining fluorescein perfused retinal whole mount preparations. METHODS: The mouse model of oxygen induced retinopathy consisting of a 5 day exposure to 75% oxygen from postnatal day 7 to 12 was used to produce retinal neovascularization. Fluorescein conjugated dextran angiography of retinal vasculature was performed and retinal whole mounts were prepared to score features of retinopathy. The parameters that were scored in a masked fashion included blood vessel growth, blood vessel tuft formation, extra retinal neovascularization, degree of central vasoconstriction, retinal hemorrhage, and tortuosity of vessels. Diltiazem (0.05-0.5 mg/kg/day subcutaneously for five days) was administered to mice pups during exposure to oxygen to determine if calcium channel blockade altered retinopathy. In addition, quantification of retinal neovascular nuclei was performed in a masked fashion with periodic acid Schiff (PAS) staining of frozen eye sections. RESULTS: Animals that were exposed to hyperoxia for five days had a median (25th, 75th quartile) retinopathy score of 9 (8,11) versus control animals that had a retinopathy score of 1 (0,1) with p<0.001. Subscores for blood vessel growth, blood vessel tufts, extra-retinal neovascularization, central vasoconstriction, hemorrhage, and blood vessel tortuosity were all significantly different between control and treated animals. In addition, quantification of neovascular nuclei showed a significant increase in the number of nuclei extending beyond the inner limiting membrane into the vitreous in hyperoxic treated animals. Diltiazem at doses of 0.2 and 0.5 mg/kg/day improved the retinopathy as measured by the total retinopathy score [5 (4,6) and 4 (3.75,5.25), respectively]. The average number of extraretinal neovascular nuclei per retinal section (mean +/-standard deviation) was significantly decreased by diltiazem at doses of 0.2 and 0.5 mg/kg/day (31.4+/-18.8 and 20.9+/-6.9, respectively) when compared to hyperoxic treated animals (56.1+/-21.5). CONCLUSIONS: Diltiazem reduces oxygen induced retinopathy in the mouse as measured by a scoring system based on a retinal whole mount method of retinal neovascularization and by quantification of extra retinal neovascular nuclei.
Animals↗
A clinical perspective on retinal neovascularization research.
Past research on retinal neovascularization forms the basis for our current primary and secondary preventive approaches toward its treatment. Several obstacles will probably delay the clinical application of angiogenic or antiangiogenic factors once these factors are satisfactorily identified. In the near future, however, the Early Treatment Diabetic Retinopathy Study should at least provide further insight into primary preventive efforts against the diabetic neovascular process. Overall, it appears that clinicians in the future must continue to rely on current modalities for the treatment of retinal neovascularization. Although new laser protocols or medications may be recommended, specific therapy targeted at the basic underlying mechanism of angiogenesis still seems to be in the distant future.
Angiogenesis Inducing Agents↗
Breakdown of the blood-retinal barrier in a model of retinal neovascularization.
Breakdown in the blood-retinal barrier occurs in retinal neovascularization in a number of diseases. To study the anatomic basis of this breakdown, we examined retinal neovascularization induced by injection of 250,000 homologous fibroblasts into the vitreous cavity of pigmented rabbits. Neovascularization is evident by electron microscopy in this model 3 days after fibroblast injection. Fluorescein angiography followed by intravenous horseradish peroxidase (HRP) injection was performed prior to enucleation on 2, 3, 5, 7, and 14 days after fibroblast injection. Fluorescein leakage from retinal vessels occurs early (at day 1) and persists as the neovascularization progresses. The leakage in the early stages is concentrated near puckers from the medullary wings. In the later stages, fluorescein leakage is most prominent in the developing tips of the new vessels. Horseradish peroxidase was not observed to leak from the lumen of new vessels. "Gaps" or separations in the endothelial cell junctions were not observed in developing vessels. The breakdown of the blood-retinal barrier in this model of retinal neovascularization is therefore selective, (ie, fluorescein leaks but not HRP) and it is not due to gaps or fenestrations between endothelial cells in developing vessels.
Animals↗
VEGF164-mediated inflammation is required for pathological, but not physiological, ischemia-induced retinal neovascularization.
Hypoxia-induced VEGF governs both physiological retinal vascular development and pathological retinal neovascularization. In the current paper, the mechanisms of physiological and pathological neovascularization are compared and contrasted. During pathological neovascularization, both the absolute and relative expression levels for VEGF164 increased to a greater degree than during physiological neovascularization. Furthermore, extensive leukocyte adhesion was observed at the leading edge of pathological, but not physiological, neovascularization. When a VEGF164-specific neutralizing aptamer was administered, it potently suppressed the leukocyte adhesion and pathological neovascularization, whereas it had little or no effect on physiological neovascularization. In parallel experiments, genetically altered VEGF164-deficient (VEGF120/188) mice exhibited no difference in physiological neovascularization when compared with wild-type (VEGF+/+) controls. In contrast, administration of a VEGFR-1/Fc fusion protein, which blocks all VEGF isoforms, led to significant suppression of both pathological and physiological neovascularization. In addition, the targeted inactivation of monocyte lineage cells with clodronate-liposomes led to the suppression of pathological neovascularization. Conversely, the blockade of T lymphocyte-mediated immune responses with an anti-CD2 antibody exacerbated pathological neovascularization. These data highlight important molecular and cellular differences between physiological and pathological retinal neovascularization. During pathological neovascularization, VEGF164 selectively induces inflammation and cellular immunity. These processes provide positive and negative angiogenic regulation, respectively. Together, new therapeutic approaches for selectively targeting pathological, but not physiological, retinal neovascularization are outlined.
Animals↗