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Miho Nozaki

Publications and source records attributed to Miho Nozaki.

13 recordsLinked to original sources
PubMed2006

Corneal avascularity is due to soluble VEGF receptor-1.

Corneal avascularity-the absence of blood vessels in the cornea-is required for optical clarity and optimal vision, and has led to the cornea being widely used for validating pro- and anti-angiogenic therapeutic strategies for many disorders. But the molecular underpinnings of the avascular phenotype have until now remained obscure and are all the more remarkable given the presence in the cornea of vascular endothelial growth factor (VEGF)-A, a potent stimulator of angiogenesis, and the proximity of the cornea to vascularized tissues. Here we show that the cornea expresses soluble VEGF receptor-1 (sVEGFR-1; also known as sflt-1) and that suppression of this endogenous VEGF-A trap by neutralizing antibodies, RNA interference or Cre-lox-mediated gene disruption abolishes corneal avascularity in mice. The spontaneously vascularized corneas of corn1 and Pax6+/- mice and Pax6+/- patients with aniridia are deficient in sflt-1, and recombinant sflt-1 administration restores corneal avascularity in corn1 and Pax6+/- mice. Manatees, the only known creatures uniformly to have vascularized corneas, do not express sflt-1, whereas the avascular corneas of dugongs, also members of the order Sirenia, elephants, the closest extant terrestrial phylogenetic relatives of manatees, and other marine mammals (dolphins and whales) contain sflt-1, indicating that it has a crucial, evolutionarily conserved role. The recognition that sflt-1 is essential for preserving the avascular ambit of the cornea can rationally guide its use as a platform for angiogenic modulators, supports its use in treating neovascular diseases, and might provide insight into the immunological privilege of the cornea.

Animals↗
PubMed2006

Drusen complement components C3a and C5a promote choroidal neovascularization.

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in industrialized nations, affecting 30-50 million people worldwide. The earliest clinical hallmark of AMD is the presence of drusen, extracellular deposits that accumulate beneath the retinal pigmented epithelium. Although drusen nearly always precede and increase the risk of choroidal neovascularization (CNV), the late vision-threatening stage of AMD, it is unknown whether drusen contribute to the development of CNV. Both in patients with AMD and in a recently described mouse model of AMD, early subretinal pigmented epithelium deposition of complement components C3 and C5 occurs, suggesting a contributing role for these inflammatory proteins in the development of AMD. Here we provide evidence that bioactive fragments of these complement components (C3a and C5a) are present in drusen of patients with AMD, and that C3a and C5a induce VEGF expression in vitro and in vivo. Further, we demonstrate that C3a and C5a are generated early in the course of laser-induced CNV, an accelerated model of neovascular AMD driven by VEGF and recruitment of leukocytes into the choroid. We also show that genetic ablation of receptors for C3a or C5a reduces VEGF expression, leukocyte recruitment, and CNV formation after laser injury, and that antibody-mediated neutralization of C3a or C5a or pharmacological blockade of their receptors also reduces CNV. Collectively, these findings establish a mechanistic basis for the clinical observation that drusen predispose to CNV, revealing a role for immunological phenomena in angiogenesis and providing therapeutic targets for AMD.

Aged, 80 and over↗
PubMed2006

Loss of SPARC-mediated VEGFR-1 suppression after injury reveals a novel antiangiogenic activity of VEGF-A.

VEGF-A promotes angiogenesis in many tissues. Here we report that choroidal neovascularization (CNV) incited by injury was increased by excess VEGF-A before injury but was suppressed by VEGF-A after injury. This unorthodox antiangiogenic effect was mediated via VEGFR-1 activation and VEGFR-2 deactivation, the latter via Src homology domain 2-containing (SH2-containing) tyrosine phosphatase-1 (SHP-1). The VEGFR-1-specific ligand placental growth factor-1 (PlGF-1), but not VEGF-E, which selectively binds VEGFR-2, mimicked these responses. Excess VEGF-A increased CNV before injury because VEGFR-1 activation was silenced by secreted protein, acidic and rich in cysteine (SPARC). The transient decline of SPARC after injury revealed a temporal window in which VEGF-A signaling was routed principally through VEGFR-1. These observations indicate that therapeutic design of VEGF-A inhibition should include consideration of the level and activity of SPARC.

Angiogenesis Inhibitors↗
PubMed2006

[Incidence and risk factors of intraocular pressure elevation after triamcinolone acetonide administration for macular disorders].

PURPOSE: We investigated the incidence and risk factors of intraocular pressure (IOP) elevation following triamcinolone administration for macular disorders. METHODS: Intravitreal or posterior sub-Tenon's injections of triamcinolone acetonide were conducted on 119 eyes with macular disorders. The change in IOP was followed for all cases. Risk factors for IOP elevation were examined regarding causal disease, history of vitrectomy, methods of injection, frequency of injection, refractive power, and age. RESULT: The difference between the mean baseline IOP (13.0 +/- 2.9 mmHg) and the maximum mean IOP (21.5 +/- 9.8 mmHg) was statistically significant (p< 0.0001). The final mean IOP was 15.1 +/- 3.6 mmHg. Forty-one eyes (34.5%) had IOP elevation over 21 mmHg during the follow-up. Fifty-nine eyes (49.6%) showed pressure elevation of over 5 mmHg. One eye (1%) required trabeculotomy to control the IOP. Risk factors for the IOP elevation included younger age, high myopia, no history of vitrectomy, and multiple injections. CONCLUSION: Careful follow-up of the IOP is required after triamcinolone acetonide injections.

Age Factors↗
PubMed2006

[Acromegalic cardiomyopathy manifesting as asymptomatic ventricular premature contractions at regular medical check up: a case report].

A 32-year-old Japanese male visited our hospital on May 20, 2004 because of ventricular premature contractions detected at a regular medical check up. He had been asymptomatic with adequate exercise capacity. However, echocardiography findings and Holter monitoring showed impaired left ventricular systolic function associated with left ventricular dilation and non-sustained ventricular tachycardia on June 26. Coronary angiography did not show significant stenosis. Different types of non-sustained ventricular tachycardia could be induced by an electrophysiologic test, but not sustained ventricular tachycardia. The physical findings, such as enlargement of the nose, lips, hands and feet, suggested endocrinologic abnormalities, and growth hormone and somatomedin-C levels were elevated. Therefore, the final diagnosis was cardiomyopathy caused by acromegaly.

Acromegaly↗
PubMed2005

Suppression of laser-induced choroidal neovascularization by posterior sub-tenon administration of triamcinolone acetonide.

PURPOSE: To evaluate the inhibitory effect of triamcinolone acetonide (TA) on choroidal neovascularization (CNV) by posterior sub-Tenon administration using a laser-induced CNV model in the rat. METHODS: Experimental CNV was induced by laser photocoagulation in Brown-Norway male rats. Experimental eyes received posterior sub-Tenon administration of either 2 mg (n = 10) or 0.5 mg (n = 8) of TA. Control eyes (n = 10) received posterior sub-Tenon administration of isotonic sodium chloride solution. Two weeks after treatment, CNV was evaluated by fluorescein angiography and histopathological examination. Concentrations of TA in the vitreous, retina, and choroid were determined by high-performance liquid chromatography at 3 and 7 days after posterior sub-Tenon administration. RESULTS: The eyes treated with 2 mg of TA showed statistically significant inhibition of fluorescein leakage by fluorescein angiography, as compared with control eyes and eyes treated with 0.5 mg of TA (P < 0.01). The thickness of CNV membranes in eyes treated with 2 mg of TA also decreased statistically significantly, as compared with control eyes (P < 0.01). TA was detected in the vitreous, retina, and choroid 3 days after administration and in the choroid 7 days after administration. CONCLUSIONS: Posterior sub-Tenon administration of TA may be useful to treat CNV.

Animals↗
PubMed2003

Pyomyositis as a focus of infection in hematological disorders: a report of 3 cases.

The cases of 3 patients with pyomyositis associated with hematological disorders are reported. A 40-year-old man in the blastic phase of chronic myelogenous leukemia and 2 men aged 46 and 71 years with neutropenia due to myelodysplastic syndromes all reported high fever and severe local myalgia and had marked elevation of C-reactive protein. Magnetic resonance imaging revealed muscle abscesses or fasciitis, and the findings led to the diagnosis of pyomyositis. Methicillin-resistant Staphylococcus aureus was isolated from the abscesses of 2 patients, and surgical drainage proved more effective than did antimicrobial agents. It should be recognized that pyomyositis is a possible source of infection in patients with hematological disorders.

Adult↗
PubMed2003

Scleral plug of biodegradable polymers containing tacrolimus (FK506) for experimental uveitis.

PURPOSE: To evaluate the efficacy of a biodegradable polymeric scleral plug containing the immunosuppressive agent, FK506, in a rabbit model for experimental uveitis. METHODS: The scleral plugs were prepared by dissolving poly(DL-lactide-co-glycolide; PLGA) and FK506 (weight, 8.5 mg; length, 5 mm; 1% FK506). The release of FK506 was evaluated in vitro by spectrophotometry on days 1, 3, 7, 14, 21, and 35. In vivo, FK506 concentrations of the vitreous were measured by high performance liquid chromatography 2 and 4 weeks after intravitreous plug implantation in pigmented rabbits. Sixteen pigmented rabbits were immunized twice subcutaneously with 10 mg of Mycobacterium tuberculosis H37Ra antigen. Twelve days later, the right eyes of all rabbits were challenged with an intravitreal injection of 50 micro g of antigen. After the first challenge, the 16 eyes of 16 pigmented rabbits were divided into two groups. Scleral plugs were implanted into the vitreous of the right eye of eight rabbits. Eight control rabbits received a sham device. The aqueous protein concentrations and cell counts were determined on postchallenge days 7, 14, and 28. To simulated chronic inflammation, the eyes were rechallenged with intravitreal antigen on day 14 and were observed for 1 month. Inflammation of the anterior chamber and the vitreous were graded clinically by two masked observers. Retinal function was evaluated by electroretinography (ERG) and histologic examination. RESULTS: Clinical scores (anterior chamber cells, flare, and vitreous opacity) showed that treated eyes had significantly less inflammation than untreated eyes (P<0.001). Quantitative analysis of inflammatory cells (P<0.001) and protein concentrations (P<0.0001) in the anterior chamber showed significant decreases in treated eyes. Histopathologic examination showed marked inflammation and tissue disorganization in the untreated eyes. No retinal toxicity was detected, histopathologically and electroretinographically. After antigen rechallenge, inflammation in experimental eyes was still less than in control eyes. CONCLUSIONS: Intravitreal sustained-release of FK506 from a biodegradable polymeric scleral plug was highly effective in suppressing the inflammation of experimental uveitis in a rabbit model for at least 6 weeks. This device may be useful in the management of patients with severe chronic uveitis.

Absorbable Implants↗
PubMed2002

Optical coherence tomographic findings of the anterior segment after nonpenetrating deep sclerectomy.

PURPOSE: To evaluate the efficacy of optical coherence tomography for the analysis of anterior segment after glaucoma surgery. DESIGN: Interventional case report. METHODS: In a 79-year-old man with primary open-angle glaucoma, optical coherence tomography was performed on the left eye after nonpenetrating deep sclerectomy. RESULTS: Optical coherence tomography showed thinning of the conjunctiva over the filtering bleb, presence of a space under the scleral flap that is considered as a lake, and presence of fibrous tissue in the bleb. CONCLUSION: This case indicates that optical coherence tomography, a noninvasive, noncontact optical imaging modality, may be useful for analysis of the anterior segment after glaucoma surgery.

Aged↗
PubMed2002

Late-onset laser in situ keratomileusis (LASIK) flap dehiscence during retinal detachment surgery.

PURPOSE: To report a case of laser in situ keratomileusis (LASIK) flap dehiscence during retinal detachment surgery 7 months after uneventful refractive surgery. DESIGN: Interventional case report. METHODS: A 47-year-old man noticed a defect of the upper visual field in his right eye 7 months after a LASIK procedure. The fundus showed rhegmatogenous retinal detachment, and a scleral buckling procedure was performed. During the buckling procedure, the corneal flap became detached. RESULTS: At completion of the buckling procedure, the detached corneal flap was carefully raised and the exposed corneal stroma was cleansed of any residual epithelial cells or red blood cells with irrigation using balanced salt solution. One day after the operation, the LASIK flap was repositioned, the cornea had cleared, and the retina was reattached. CONCLUSIONS: As LASIK increases in popularity, the complication we have reported may become more common. We suggest that a retinal detachment surgery should be performed with careful avoidance of corneal trauma even if a long time has passed since the LASIK procedure.

Corneal Stroma↗
PubMedDate not supplied

Enhanced expression of adhesion molecules of the retinal vascular endothelium in spontaneous diabetic rats.

Otsuka Long-Evans Tokushima Fatty (OLETF) rats are a spontaneously diabetic strain with clinical features resembling those of human noninsulin-dependent diabetes mellitus. These rats show increased leukocyte entrapment in the retina. The present study was designed to investigate the immunolocalization of intercellular adhesion molecules-1 (ICAM-1) and P-selectin in the retinas of OLETF rats. Four 72-week-old male OLETF rats and 4 age- and sex-matched Long-Evans Tokushima Otsuka (LETO) control rats were used. Western blot analysis and immunohistochemical study were performed using an anti-P-selectin monoclonal antibody (mAb) and an anti-ICAM-1 mAb. Western blot analysis showed increased expression of both ICAM-1 and P-selectin in the retinas of OLETF rats. Immunohistochemically, OLETF rats expressed greater amounts of ICAM-1 and P-selectin in the retinal vascular endothelium than did LETO rats. These findings demonstrated the upregulation of ICAM-1 and P-selectin in the retina of OLETF rats. The enhanced expression of these adhesion molecules might participate in the pathogenesis of early diabetic microangiopathy in the retina.

Animals↗