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PubMedDate not supplied

Expression of ephrin in retinal neovascularization and iris rubeosis.

We investigated expression of ephrin-B2 and Eph-B4 in the retinal tissues of six primate eyes with neovascularization and iris rubeosis secondary to laser-induced central retinal vein occlusion and in tissue from 10 human eyes with proliferative diabetic retinopathy. Two primate eyes with rubeosis and retinal neovascularization were enucleated 1, 2 and 4 weeks after the creation of central retinal vein occlusion. Antibodies were localized using the avidin-biotin reaction. In the primate eyes, ephrin-B2 was negative at I week and positive at 2 and 4 weeks in the rubeotic tissue, but was positive only at 2 weeks in the retinal neovascular membrane. Eph-B4 was negative in all the primate eye specimens. In the human tissue, ephrin-B2 was detected in two of the five eyes with rubeosis and three of the five eyes with retinal neovascularization. These data suggest that ephrin-B2 is a key regulator of neovascularization.

Angiogenic Proteins↗
PubMed1982

Branch vein occlusion. Retinal neovascularization outside the involved segment.

Three hundred sixty-six cases of branch vein occlusion entered within the multicenter Branch Vein Occlusion Randomized Clinical Trial have been reviewed. Four cases that developed retinal neovascularization outside of the retinal area involved with the occlusion have been documented by photography and fluorescein angiography.

Aged↗
PubMed1995

Sneddon's syndrome with bilateral peripheral retinal neovascularization.

A 27-year old woman is presented with a five year old history of Sneddon's syndrome in whom recently peripheral retinal neovascularization in both eyes was discovered. Sneddon's syndrome is a rare clinical entity first described in 1965 and characterized by typical skin lesions (livedo reticularis) and cerebrovascular lesions occurring at early age. Central retinal artery occlusions have been reported twice in Sneddon-patients, but peripheral retinal capillary occlusions and neovascularization have not yet been reported. The role of the antiphospholipid antibodies in this association is discussed.

Adult↗
PubMed2005

Does insulin-like growth factor 1 contribute in red blood cell transfusions to the pathogenesis of retinopathy of prematurity during retinal neovascularization?

BACKGROUND: Red blood cell (RBC) transfusions are associated with the development of retinopathy of prematurity (ROP). During the period of retinal neovascularization a rise of insulin-like growth factor 1 (IGF-1) may trigger rapid growth of new blood vessels. OBJECTIVES: To study endocrine factors in RBC transfusions that might be of importance for ROP. METHODS: IGF-1, IGF-2 and their binding proteins 1-3 (IGFBP-1-3) were determined by radioimmunoassays in 7 very-low-birthweight (VLBW) infants with ROP >or= stage 2 receiving a RBC transfusion, in 10 controls (VLBW infants with ROP <or= stage 1, no transfusion), in supernatants of 7 RBCs and of 5 washed RBCs (WRBC). RESULTS: IGF-1 (mean +/- SD) in infants with ROP was 20.0 +/- 4.2 microg/l, in controls 35.9 +/- 15.2 microg/l (Mann-Whitney U test, p = 0.030). IGF-1 in RBC was 12.88 +/- 5.03 microg/l and in WRBC 0.45 +/- 0.74 microg/l (average of the three-course washing procedure). IGF-2 in infants with ROP was 485.67 +/- 158.73 microg/l, in controls 389.9 +/- 102.8 microg/l (not significant), in RBC 109.50 +/- 117.89 microg/l, in WRBC 61.07 +/- 30.0 microg/l. Except for IGFBP-3 other IGFBPs were barely or not detectable in RBC or WRBC. CONCLUSIONS: Considering lower IGF-1 concentrations in preterm infants than in adults (factor 20), the IGF-1 in RBC transfusions is equivalent to a single dose of 1 microg/kg IGF-1 (5-10% of the adult dose with proved metabolic responses). Endocrinological relationships between the donor's load and the acceptor's individual features are a new aspect of potential side effects of RBC transfusions. Further research is necessary to clarify the share of the described IGF administration on the development of ROP.

Erythrocyte Transfusion↗
PubMed1978

A new approach to the problem of retinal neovascularization.

Tumor cells introduced into the rabbit vitreous produced a form of retinal neovascularization, but only when the tumor cells were in direct contact with the vascularized retina. This contrasted with the production of neovascularization at a distance of several millimeters in other angiogenesis models. An extract of adult rabbit vitreous was found to inhibit the growth of limbal neovascularization induced by tumors implanted in the rabbit corneal stroma. The experimental model of retrolental fibroplasia provides a bioassay to investigate further the apparent inhibitory substances in the vitreous.

Angiogenesis Inducing Agents↗
PubMed2005

Adeno-associated virus-mediated expression of vascular endothelial growth factor peptides inhibits retinal neovascularization in a mouse model of oxygen-induced retinopathy.

Vascular endothelial growth factor (VEGF) has been demonstrated to be a key stimulator of retinal neovascularization (NV), the most common cause of severe and progressive vision loss. In this study, we used a mouse model of oxygen-induced retinopathy (OIR) to explore the potential of gene expression and secretion of short VEGF peptides as a treatment. Peptide-encoding fragments of exons 6 and 7 of the VEGF gene were cloned into a recombinant adeno-associated virus (rAAV) vector. Expression of each peptide in vector-injected eyes was confirmed by reverse transcription-polymerase chain reaction and Western blot analysis. Intravitreal injection of each rAAV vector inhibited retinal NV by 71-83% (p < 0.001) compared with contralateral control eyes in the OIR mouse. Injection and expression of these peptides did not seem to affect the normal appearance of the retina. The results demonstrated that exon 6- and 7-derived VEGF peptides effectively inhibited oxygen-induced retinal NV. Therefore, these VEGF peptides have potential in the treatment of angiogenesis-associated retinal diseases in humans.

Animals↗
PubMed2003

Extensive retinal neovascularization as a late finding in human immunodeficiency virus-infected patients with immune recovery uveitis.

Sixteen human immunodeficiency virus (HIV)-infected patients with inactive cytomegalovirus (CMV) retinitis who had discontinued systemic anti-CMV therapy while receiving highly active antiretroviral therapy (HAART) were prospectively observed. Fifteen patients developed immune recovery uveitis (IRU); 3 of the patients developed extensive retinal neovascularization, 1 of whom required vitrectomy for recurrent vitreous hemorrhages. These late complications indicate a need for continued ophthalmologic follow-up of HIV-infected patients who have a history of CMV retinitis, even for individuals who have not required anti-CMV therapy for >4 years.

Adult↗
PubMed2003

Knockout of insulin and IGF-1 receptors on vascular endothelial cells protects against retinal neovascularization.

Both insulin and IGF-1 have been implicated in control of retinal endothelial cell growth, neovascularization, and diabetic retinopathy. To precisely define the role of insulin and IGF-1 signaling in endothelium in these processes, we have used the oxygen-induced retinopathy model to study mice with a vascular endothelial cell-specific knockout of the insulin receptor (VENIRKO) or IGF-1 receptor (VENIFARKO). Following relative hypoxia, VENIRKO mice show a 57% decrease in retinal neovascularization as compared with controls. This is associated with a blunted rise in VEGF, eNOS, and endothelin-1. By contrast, VENIFARKO mice show only a 34% reduction in neovascularization and a very modest reduction in mediator generation. These data indicate that both insulin and IGF-1 signaling in endothelium play a role in retinal neovascularization through the expression of vascular mediators, with the effect of insulin being most important in this process.

Animals↗
PubMed1993

Clinical features of autosomal dominant retinitis pigmentosa with rhodopsin gene codon 17 mutation and retinal neovascularization in a Japanese patient.

A 49-year-old Japanese man had autosomal dominant retinitis pigmentosa with a point mutation in codon 17 of the rhodopsin gene, resulting in a threonine-to-methionine change, and retinal neovascularization in both eyes. Pigmentary degeneration mainly in the inferior area of the fundus, and severe loss in the upper portion of the visual field were observed. Moderately preserved rod and cone functions were demonstrated by electroretinograms. These findings differed from those of Japanese and white patients with autosomal dominant retinitis pigmentosa with a codon 347 mutation and were almost the same as those of white patients with the codon 17 mutation. Our study indicates that phenotypic similarities exist among patients with the same mutation, but of different racial backgrounds. The neovascularization in the right eye diminished over a two-year period in conjunction with the progression of retinal degeneration.

Adaptation, Ocular↗
PubMed2000

Retinal neovascularization is prevented by blockade of the renin-angiotensin system.

Both angiotensin II and vascular endothelial growth factor are angiogenic agents that have recently been implicated in the pathogenesis of proliferative diabetic retinopathy. In this study, retinal neovascularization was examined in a model of retinopathy of prematurity with the use of neonatal transgenic (mRen-2)27 rats, which overexpress renin in tissues, and Sprague-Dawley rats. Blockers of the renin-angiotensin system were administered during the neovascularization period. The ACE inhibitor lisinopril and the angiotensin type 1 receptor antagonist losartan both increased retinal renin levels and prevented inner retinal blood vessel growth. Quantitative in situ hybridization revealed that the expression of vascular endothelial growth factor and its type 2 receptor in the inner retina and proliferating blood vessels were increased in rats with retinopathy of prematurity. Lisinopril reduced both retinal vascular endothelial growth factor and its type 2 receptor mRNA in retinopathy of prematurity rats, whereas losartan had no effect. It is predicted that agents that interrupt the renin-angiotensin system may play an important role as retinoprotective agents in various forms of proliferative retinopathy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2003

Specificity of subnormal deltaPO2 for retinal neovascularization in experimental retinopathy of prematurity.

PURPOSE: To test the hypothesis that in an experimental model of retinopathy of prematurity (ROP) rat pups that are at risk for but do not have retinal neovascularization (NV) exhibit a normal oxygenation response to a hyperoxic inhalation challenge. METHODS: Newborn Sprague-Dawley rats were raised under two varied oxygen conditions (50/10 or 40/15, indicating percent of oxygen in the air on alternate days) for 14 days and then allowed to recover in room air. Functional magnetic resonance imaging was used to determine the retinal oxygenation response (increase in partial oxygen pressure in the vitreous over the room air value, or deltaPO(2), in mm Hg) to hyperoxic inhalation challenge. Adenosine diphosphatase (ADPase)-stained retinas were analyzed to determine the NV incidence and severity. RESULTS: On postnatal day (P)20, the 40/15 procedure produced significantly (P < 0.05) lower incidence of NV than the 50/10 protocol (8% vs. 99%, respectively). Retinal deltaPO(2) during carbogen breathing of the 40/15 animals that did not have evidence of NV was not different (P > 0.05) from that of normal age-matched animals; later time points were not examined. At P26 and P34, in 50/10 rats that no longer had NV, retinal deltaPO(2)s during carbogen breathing were significantly (P < 0.05) lower than that of age-matched control pups. At P34 in control rats, but not in 50/10 rats, deltaPO(2) was 61% greater (P < 0.05) during carbogen breathing than during oxygen breathing. CONCLUSIONS: The results from 40/15 experiments, together with the authors' previous data in 50/10 rats, which documented subnormal retinal deltaPO(2) before and during NV, provides additional support that subnormal retinal oxygenation to an inhalation challenge is an important event associated with the development of NV. In addition, 50/10 rats that no longer demonstrated NV had a persistent subnormal retinal deltaPO(2), suggesting a continuing risk of development of additional retinal complications after resolution of the NV in ROP.

Animals↗
PubMed1988

Peripheral retinal neovascularization and rubeosis iridis after a bilateral circular buckling operation.

This report describes a young high-myopic patient who developed rubeosis iridis with peripheral retinal neovascularization one year after a circular buckling operation. Subsequently, vitreous bleeding and exudation led to traction retinal detachment which was treated successfully by anterior vitrectomy and cryopexy. It is suggested that this case represents a mild form of anterior-segment ischemia, combined with peripheral retinal ischemia.

Child↗
PubMed2002

Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization.

Adults maintain a reservoir of hematopoietic stem cells that can enter the circulation to reach organs in need of regeneration. We developed a novel model of retinal neovascularization in adult mice to examine the role of hematopoietic stem cells in revascularizing ischemic retinas. Adult mice were durably engrafted with hematopoietic stem cells isolated from transgenic mice expressing green fluorescent protein. We performed serial long-term transplants, to ensure activity arose from self-renewing stem cells, and single hematopoietic stem-cell transplants to show clonality. After durable hematopoietic engraftment was established, retinal ischemia was induced to promote neovascularization. Our results indicate that self-renewing adult hematopoietic stem cells have functional hemangioblast activity, that is, they can clonally differentiate into all hematopoietic cell lineages as well as endothelial cells that revascularize adult retina. We also show that recruitment of endothelial precursors to sites of ischemic injury has a significant role in neovascularization.

Animals↗
PubMed1979

Disk and peripheral retinal neovascularization secondary to talc and cornstarch emboli.

A 30-year-old man was examined because of blurred vision. The symptoms had occurred immediately after the patient had injected himself intravenously with crushed, unfiltered, methylphenidate HCl (Ritalin) tablets. Fine yellow-white crystals were scattered throughout the retin of both eyes. The crystals were presumed to be talc emboli. Disk and peripheral retinal neovascularization were present. Fluorescein angiography revealed widespread retinal capillary nonperfusion. This is the first reported case, to the best of my knowledge, of disk neovascularization occurring after intravenously injected, crushed, unfiltered, methylphenidate HCl tablets.

Adult↗
PubMed2002

Detection of retinal neovascularizations using 45 degrees and 60 degrees photographic fields with varying 45 degrees fields simulated on a 60 degrees photograph.

PURPOSE: To compare the effectiveness of one- and two-field 45 degrees and 60 degrees fundus photography for detection of retinal neovascularizations (NVEs); to compare the detection of NVEs in macular 45 degrees fields centred on the fovea, between the fovea and the disc and with the nasal border along the nasal disc margin with that in standard 60 degrees one- and two-fields. METHODS: Two ophthalmologists assessed red-free, black and white screening and follow-up photographs of 58 out of a total 72 patients referred for treatment for NVEs over the 3 year period 1997-99. The assessment included analysis of the numbers, sizes and locations of NVEs identified in different photographic fields defined by a transparent grid placed over two standard 60 degrees fields. RESULTS: Testing of 45 degrees macular fields disclosed 59/81 (73%), 50/81 (62%) and 64/81 (79%), respectively, of NVEs detected in a 60 degrees fovea-centred photograph. Kappa values for detecting at least one NVE, when present, were 0.62 (95% CI 0.40-0.83), 0.38 (95% CI 0.19-0.57) and 0.83 (95% CI 0.62-0.99). The corresponding figures when compared with two-field 60 degrees photography were 59/111 (53%), 50/111 (45%) and 64/111 (58%), respectively. One macula-centred 60 degrees field disclosed 81/111 (73%) of NVEs detected by 60 degrees two-field photography with an additional optic disc-centred field. Two-field 45 degrees photography disclosed 86/111 (77%) of NVEs detected by two-field 60 degrees photography. A total of 90% of NVEs detected in the optic disc-centred 60 degrees field only were also detected in the corresponding 45 degrees field. CONCLUSION: One-field 45 degrees photography cannot be recommended as a screening method for diabetic retinopathy. Two-field 45 degrees photography (macula-centred and disc-centred fields) disclosed 77% of NVEs detected by the corresponding two-field 60 degrees photography.

Adult↗
PubMed1996

Corneal coloboma, aphakia and retinal neovascularization with anterior segment dysgenesis (Peters' anomaly).

An infant with bilateral Peters' Anomaly, with corneal opacification in the right eye and an opacification with an axial defect in the left also had an associated hydrocephalus and cardiac anomalies that proved fatal; histopathology of the right eye showed retinal neovascularization in addition to findings consistent with a diagnosis of Peters' Anomaly; in the left eye, pathologic findings were suggestive of a corneal coloboma associated with aphakia.

Abnormalities, Multiple↗
PubMed2005

Inhibition of vascular endothelial growth factor-induced retinal neovascularization by retinoic acid in experimental retinopathy of prematurity.

Vascular endothelial growth factor (VEGF) has an important role in the pathogenesis of retinopathy of prematurity (ROP) and inhibition of VEGF expression in the neovascular phase might prevent destructive neovascularization in ROP. It is suggested that retinoids exert a highly potent antiangiogenic activity by inhibiting VEGF expression. The aim of this study was to demonstrate the preventive effect of retinoic acid (RA) on the VEGF-induced retinal neovascularization in a rat model of ROP. Wistar albino rats were placed into incubators at birth 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 and received either an intraperitoneal injection of RA (5 mg/kg/day) (n=9) or saline (n=4) daily for six days, and sacrificed at 21 days. Other rats (n=4) were raised in room air and served as age-matched controls. The globe of each eye was cut through the cornea and embedded in paraffin. Serial sections were stained with hematoxylin-eosin for quantification of neovascular nuclei. The avidin-biotin peroxidase method was performed for evaluation of VEGF expression. The average number of neovascular nuclei was significantly lower in the control group compared to that in the ROP groups. In addition, it significantly decreased in the RA-treated ROP group compared to that of the saline-administrated ROP group. VEGF immunostaining was overall negative in room air-exposed rats. The VEGF immunostaining score significantly decreased in the RA-treated ROP group compared to that in the saline-administered ROP group. RA treatment might be beneficial in preventing neovascularization resulting from oxygen-induced retinopathy by downregulation of VEGF expression.

Animals↗
PubMed2006

[The effect of Sairei-to on oxygen-induced retinal neovascularization in the neonatal rat].

PURPOSE: To study the effect of Sairei-to (ST), a Japanese traditional medicine, on oxygen-induced retinopathy (OIR) in rats. METHODS: OIR was induced by maintaining Sprague-Dawley neonatal rats in 80% oxygen for 12 days. The rats were treated once daily with oral administration of 0.75 g/kg (n = 9), 1.5 g/kg (n = 13) of ST in water, or water alone (WA, n = 13) at 5 mL/ kg body weight from day 6 to day 17. On day 18, retinal samples were collected. Retinal neovascularization (NV) was assessed by the NV score, and by the percentage of avascular area (% AVA), using a method previously reported. The number of severe retinal NV cases (NV > or = 9) was compared. The retinal vascular endothelial growth factor (VEGF) concentrations were measured with an immunoassay kit, at 0, 12, 24, 72 and 144 hours after oxygenation. RESULTS: NV score and % AVA decreased in the ST treated group compared to the WA group. However, severe NV was seen in five cases of WA and in one case of the ST treated group. Thus severe NV was inhibited significantly by ST treatment (p = 0.0185). Retinal VEGF did not differ between groups at any time points. CONCLUSION: These data suggest that severe NV in OIR is inhibited by ST treatment.

Animals↗