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Acute Disease↗

Roentgenology-pathology correlative study of neovascularity.

In an attempt to evaluate the histologic picture of what is shown on angiograms as neovascularity, several benign and malignant tumors were examined. New vessels (neovascularity) are large capillaries or sinusoids, and neither contain smooth muscle in their walls. The walls may contain some fibrous connective tissue. Puddling, laking, and staining represent the collection of contrast medium in small capillaries or sinusoids. Some tumors, such as hemangioma of the liver, cystadenoma of the pancreas, and angiomyolipoma of the kidney contained abnormal vascularity, but this was not composed of vessels which had arisen or developed anew, as there was smooth muscle in their walls, and this indicates that those vessels had been there from birth. In xanthogranulomatous pyelonephritis and chronic renal disease, the appearance of increased vascularity is the result of rearrangement of the normal vascular structures.

Angiography↗

Effects of sustained hyperoxia on revascularization in experimental retinopathy of prematurity.

PURPOSE: To investigate the effects of prolonged hyperoxia on vascular recovery and glia survival after experimentally induced retinopathy of prematurity (ROP) in the mouse. METHODS: The effects of hyperoxia on revascularization and vitreous neovascularization were compared between mice raised in 75% oxygen from postnatal day (P)7 to P12, followed by room air recovery and mice raised in 75% oxygen from P7 to P27. The status of astrocytes and Müller cells was evaluated by glial fibrillary acidic protein (GFAP) immunohistochemistry on retinal wholemounts and serial sections. A window of susceptibility to oxygen-induced vaso-obliteration was defined by comparing the extent of retinal vaso-obliteration resulting from 2 days of hyperoxia beginning on P7, P9, P11, P13, or P15. RESULTS: Oxygen-induced vaso-obliteration of retinal capillaries was limited to the period between birth and P15. Paradoxically, revascularization was markedly accelerated and neovascularization markedly reduced in mice maintained in prolonged hyperoxia (P7-P27) compared with mice recovering in room air. The extended use of 75% oxygen during the recovery period was associated with preservation of astrocytes and Müller cells in the avascular retina. CONCLUSIONS: The antiangiogenic effect of hyperoxia on retinal capillaries is strongly dependent on postnatal age. A protocol of continuous 75% supplemental oxygen accelerates recovery of inner retinal vasculature and prevents vitreous neovascularization, by a mechanism that may involve preservation of inner retinal glia.

Animals↗

A fucosylated chondroitin sulfate from echinoderm modulates in vitro fibroblast growth factor 2-dependent angiogenesis.

Fucosylated chondroitin sulfate (FucCS), a glycosaminoglycan obtained from sea cucumber, has the same structure as mammalian chondroitin sulfate, but some of the glucuronic acid residues display sulfated fucose branches. This new polysaccharide has a more favorable effect than heparin on vascular cell growth. It inhibits smooth muscle cell proliferation as heparin, and it has a potent enhancing effect on endothelial cell proliferation and migration in the presence of heparin-binding growth factors. We now extend our studies to the effect of this glycosaminoglycan on endothelial cells to an in vitro angiogenesis model on Matrigel. FucCS, in the presence of fibroblast growth factor-2 (FGF-2), strongly increases the capacity of endothelial cells to form vascular tubes on Matrigel with a well-organized capillary-like network and typical closed structures. Comparison between the activity of native and chemically modified chondroitin sulfate from sea cucumber reveals that the sulfated fucose branches are the structural motif for the proangiogenic activity. Heparin does not induce angiogenesis in this experimental model. We also have evidence for the proposition that endothelial cell proliferation is not the sole event involved in the in vitro FGF-2-induced angiogenesis. It implies a variety of other modifications of the endothelial cells and of their interaction with the extracellular matrix, such as integrin expression and actin cytoskeleton reorganization. Finally, the proangiogenic effect of FucCS, concomitant with its capacity to prevent venous and arterial thrombosis, in animal models makes this new glycosaminoglycan a promising molecule with possible beneficial effects in pathological conditions affecting blood vessels such as the neovascularization of ischemic areas.

Actins↗

Elevated vascular endothelial growth factor levels in the vitreous of patients with proliferative diabetic retinopathy.

OBJECTIVE: To detect the levels of vascular endothelial growth factor (VEGF) in the vitreous of patients with proliferative diabetic retinopathy (PDR) and to investigate the possible role of VEGF in the development of neovascularization in PDR. METHODS: Undiluted vitreous samples and fasting venous blood samples were obtained from 27 patients with PDR and 14 subjects with idiopathic macular hole who underwent pars plana vitrectomy. The concentration of VEGF was determined by quantitative enzyme-linked immunosorbent assay (ELISA). RESULTS: The level of vitreous VEGF in patients with PDR (median 0.41 ng/ml, range 0.09-11.56 ng/ml) was significantly elevated when compared with that in control subjects (median 0.017 ng/ml, range 0.008-0.04 ng/ml) (P < 0.001). The median of PDR patients' serum VEGF concentration was 0.19 ng/ml (0.090.46 ng/ml) which was far lower than vitreous VEGF concentration (P < 0.05). Vitreous VEGF concentration was higher in PDR patients with retinal detachment than that in patient without retinal detachment (P < 0.05). CONCLUSIONS: Vitreous levels of VEGF were remarkably elevated in eyes with PDR, and they were not influenced by its serum concentrations. VEGF played an important role in neovascularization of PDR.

Adult↗

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↗

Cigarette smoke-induced emphysema in guinea pigs is associated with diffusely decreased capillary density and capillary narrowing.

There is little information about whether alveolar capillaries are altered in emphysema. To examine this question, we used scanning electron microscopic morphometry of microvascular corrosion casts to evaluate capillary structure in a guinea pig model of cigarette smoke-induced emphysema. After 6 months, the mean airspace size in the smoke-exposed animals was 157 +/- 31 microns and 106 +/- 11 microns (p < 0.001) in the control (air-exposed) animals. Because previous results from our laboratory had shown differences in size and density between central and peripheral capillaries in normal guinea pigs, these two areas were sampled separately in the present study. Capillaries in the emphysematous animals were narrowed compared with those in the control animals in both the center (mean diameter, 7.51 +/- 1.95 versus 8.93 +/- 2.01 microns, p < 0.001) and periphery (mean diameter, 8.52 +/- 2.13 versus 10.15 +/- 2.16 microns, p < 0.001) of the lobule. Smoke-exposed animals had a decreased capillary density in both the center (0.73 +/- 0.06 versus 0.79 +/- 0.05, p < 0.001) and periphery (0.77 +/- 0.07 versus 0.84 +/- 0.04, p < 0.001) of the lobule. We conclude that cigarette smoke-induced emphysema is associated with a diffuse and relatively uniform narrowing of capillaries with loss of capillary density throughout the lung. These findings may reflect diffuse smoke-induced abnormalities in the alveolar wall matrix with stretching of capillaries over enlarged airspaces and may partially explain the alteration of ventilation perfusion distribution in cigarette smoke-induced emphysema.

Animals↗

Intrachoroidal dye leakage in indocyanine green fundus angiography after experimental commotio retinae.

Dye leakage in sodium fluorescein (FLUO) fundus angiography indicates damage to the blood-retinal barrier. However, dye leakage in indocyanine green (ICG) fundus angiography does not mean the same, because of the larger molecular size of the dye and impermeability of the choroidal vessels to it. The possibility of dye leakage in ICG angiography has not yet been revealed in an experimental study in which the blood-retinal barrier is undamaged. We report here that intrachoroidal dye leakage may occur in ICG angiography in an experimental model of the traumatic retinal opacity of the rabbit eye, even when the blood-retinal barrier is undamaged. This mechanism of dye leakage in ICG angiography is quite different from the leakage of FLUO angiography. Pathological choroidal vessels with increased permeability, such as choroidal neovascularization under the retinal pigment epithelium, can be observed using ICG angiography.

Animals↗

Ocular findings in children with severe clinical symptoms of homozygous sickle cell anaemia in Kaduna, Nigeria.

BACKGROUND: Sight-threatening retinopathy in Sickle Cell Disease is thought to be due mainly to vasoocclusion. Yet it is reportedly rarely found in children with Haemoglobin SS, (who most often suffer from vasoocclusion). However, earlier reports included patients with a wide range of clinical severity. AIM: To document ocular pathology in children with Haemoglobin SS with severe clinical disease. METHODS: Thirty-seven children with severe clinical disease (at least 3 vaso-occlusive episodes in one year) had detailed ocular examinations over a one-year period. RESULTS: No child (aged 3 to 13 years) had ocular symptoms. Visual acuity was abnormal in one child. Retinal pathology was found only in patients over 8 years. Neovascularization was observed in 3 eyes of 2 patients both of whom had higher than average irreversibly sickled cell counts and haemoglobin levels. Retinal and choroidal infarcts were found in 11 and 2 eyes respectively; sunburst lesions and salmon patch haemorrhages in 5 eyes each. Changes observed over the one-year period in the 32 survivors, were photocoagulation scars in one eye of a child who had undergone laser therapy and resolution of the salmon patch haemorrhages. CONCLUSION: Despite lack of visual symptoms, young children with haemoglobin SS with severe clinical symptoms can develop sight-threatening retinopathy. The possible role of autoinfarction in the causation of these lesions is discussed. Our study shows that routine yearly ophthalmological examinations are essential for children over 8 years.

Adolescent↗

Preretinal and optic nerve head neovascularization induced by photodynamic venous thrombosis in domestic pigs.

OBJECTIVE: To develop a reliable model of ischemic preretinal and optic nerve head neovascularization in young male domestic pigs. METHODS: Using laser-induced branch retinal venous obstruction assisted by photodynamic thrombosis with rose bengal, 15 of 15 treated eyes developed neovascularization of the optic nerve head and retina. All cases of neovascularization were followed up clinically for up to 12 weeks. RESULTS: Clinical, fluorescein angiographic, and histopathologic features were consistent with neovascular proliferation into the vitreous. CONCLUSIONS: Further evaluation of the long-term natural history, role of the degree of ischemia, and the effect of interventions for various types of ischemic retinopathy (eg, panretinal photocoagulation) is warranted. This model is simple and relatively inexpensive and allows easy clinical assessment.

Animals↗

Stem cell biology for vascular regeneration.

The isolation of endothelial progenitor cells (EPCs) derived from bone marrow (BM) was one epoch-making event for the recognition of neovessel formation in adults occurring as physiological and pathological responses. The finding that EPCs home to sites of neovascularization and differentiate into endothelial cells (ECs) in situ is consistent with vasculogenesis, a critical paradigm that has been well described for embryonic neovascularization, but proposed recently in adults in which a reservoir of stem or progenitor cells contribute to vascular organogenesis. EPCs have also been considered as therapeutic agents to supply the potent origin of neovascularization under pathological conditions. This chapter highlights an update of EPC biology as well as its potential use for therapeutic regeneration.

Adult↗

Retinal and disc neovascularization in Behçet's disease and efficacy of laser photocoagulation.

BACKGROUND: The vaso-occlusive episodes resulting from Behçet's disease can cause capillary dropout and vascular remodeling. Retinal and disc neovascularizations, which occur as a result of occlusive vasculitis, can cause recurrent vitreal hemorrhages and neovascular glaucoma leading to severe visual impairment. METHODS: 1080 eyes of 540 patients with Behçet's disease were examined between 1973 and 1993. Of the 912 eyes with posterior segment involvement, laser photocoagulation could be performed in 13 of 25 eyes with disc neovascularization (NVD), 12 of 22 eyes with retinal neovascularization (NVE), and 4 of 6 eyes with NVD and NVE. Laser was directed at areas of NVE and retinal capillary nonperfusion. In cases of NVD, panretinal photocoagulation was performed. RESULTS: The rate of regression of NVD was significantly greater in laser-treated eyes than in the untreated group. The results were similar in cases of NVD with NVE. In eyes with NVE which underwent laser photocoagulation, the NVE regressed. None of the treated eyes developed neovascular glaucoma during the follow-up period. Vitreous hemorrhage occurred in two laser-treated eyes. CONCLUSION: Laser photocoagulation is successful in preventing complications of retinal and disc neovascularizations. Thus, in cases of occlusive vasculitis associated with Behçet's disease, laser photocoagulation should be considered for prevention of complications such as vitreous hemorrhage and neovascular glaucoma.

Adult↗