Biomedical subjects

Miyo Matsumura

Publications and source records attributed to Miyo Matsumura.

At least 19 recordsLinked to original sources

PubMed2007

Senescence in cultured trabecular meshwork cells.

BACKGROUND: It has been suggested that replicative senescence might be involved in the pathophysiology of age-related diseases. AIM: To study the process of senescence in trabecular meshwork (TM) cells. METHODS: Porcine TM tissues were obtained and placed in primary cultures with Dulbecco's modified Eagle's medium/Ham's F-12 medium. After 2-3 weeks, migrated and proliferated TM cells were trypsinised and cultured in serial passages, and identified with fluorescein-labelled low-density lipoprotein (DiI-Ac-LDL), a marker of TM cells. Staining for senescence-related beta-galactosidase activity was performed at population doubling level (PDL) 2, 8 and 16 at pH 6. Terminal restriction fragment (TRF) length was examined by Southern blot analysis using a (32)P-labelled telomere-specific sequence (TTAGGG)(3) at each PDL. RESULTS: DiI-Ac-LDL staining revealed that most (nearly 100%) of the cells in the culture were TM cells, which were flattened in shape and positive for senescence-related beta-galactosidase staining at PDL 16. Reduction of TRF length as a function of population doubling was also shown. CONCLUSIONS: TM cells exhibited characteristics of senescence at PDL 16 in vitro. The results demonstrated that cellular senescence may be related to the pathophysiology of primary open-angle glaucoma.

Animals↗

PubMed2007

Plasma concentration of pigment epithelium-derived factor in patients with diabetic retinopathy.

CONTEXT: Pigment epithelium-derived factor (PEDF) is a strong inhibitor of angiogenesis. Eyes with diabetic retinopathy have low levels of ocular PEDF; however, the PEDF levels in the blood of diabetics have still not been determined. OBJECTIVES: Our objective was to determine the plasma levels of PEDF in diabetic patients and to determine the relationship with the stage of the diabetic retinopathy. DESIGN AND SETTING: This study was designed as a cross-sectional, institutional study. PATIENTS OR OTHER PARTICIPANTS: A total of 145 Japanese were studied; 112 had type 2 diabetes mellitus, and 33 were healthy controls. INTERVENTION: There was no intervention. MAIN OUTCOME MEASURES: The plasma level of PEDF was measured by ELISA, and the stage of diabetic retinopathy was determined by ophthalmic examinations. Clinical systemic status of diabetic patients was also examined. RESULTS: The plasma PEDF level in diabetic patients (6.68 +/- 0.54 microg/ml; mean +/- sem) was significantly higher than that in controls (4.38 +/- 0.59 microg/ml, P = 0.03), and the level was especially high in patients with proliferative diabetic retinopathy (7.78 +/- 0.98 microg/ml; n = 45; P = 0.005). The gender (P = 0.03), blood urea nitrogen (P = 0.005), and triglycerides (P = 0.04) were significant and independent determinants of plasma PEDF levels in diabetic patients. CONCLUSIONS: The PEDF level in the plasma was significantly elevated in diabetic patients, especially those with proliferative diabetic retinopathy. High levels of PEDF in the plasma may be related to the progression of diabetic retinopathy.

Adolescent↗

PubMed2007

Cytotoxic effect of spermine on retinal pigment epithelial cells.

PURPOSE: A prior study showed inactivation of ornithine-delta-aminotransferase (OAT)-deficient human retinal pigment epithelial (RPE) cells by a specific irreversible inhibitor (5-fluoromethylornithine; 5-FMO) leading to cell death, in an in vitro model of gyrate atrophy (GA) of the choroid and retina. In the present study, the cytotoxicity of metabolites of ornithine, especially spermine, in RPE cells was investigated, to clarify the mechanism of ornithine cytotoxicity in RPE cells. METHODS: RPE cells were incubated with ornithine or compounds involved in ornithine metabolic pathways. The effects on RPE cell viability and proliferative activity were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric and [(3)H]thymidine incorporation assays. Incorporation of spermine into RPE cells was examined by using [(14)C]spermine and dansyl-spermine. To assess spermine-induced RPE cell death, cells were double stained with annexin V and propidium iodide and subjected to flow cytometry. RESULTS: Ornithine, arginine, glutamate, proline, creatine, glycine, and putrescine exhibited no effects on the viability and proliferative activities of RPE cells, whereas spermidine and spermine (10 mM) inhibited [(3)H]thymidine incorporation by 13% and 89%, respectively. The inhibition of [(3)H]thymidine incorporation by spermine was dose dependent and was observed as early as 4 hours after addition. Further, spermine was incorporated and accumulated in the perinuclear region of RPE cells. Apoptotic RPE cell death was induced by spermine in a dose-dependent manner. CONCLUSIONS: The present results demonstrated that excessive spermine is cytotoxic to RPE cells and suggest that metabolites of ornithine, especially spermine, may be involved in the mechanism of RPE degeneration in GA.

Animals↗

PubMed2007

Ornithine transport via cationic amino acid transporter-1 is involved in ornithine cytotoxicity in retinal pigment epithelial cells.

PURPOSE: A prior report showed ornithine cytotoxicity in ornithine-delta-aminotransferase (OAT)-deficient human retinal pigment epithelial (RPE) cells in an in vitro model of gyrate atrophy of the choroid and retina. This study was intended to clarify the mechanism of ornithine cytotoxicity and to determine the responsible amino acid transporters. METHODS: The mRNA expression of amino acid transporters in human telomerase reverse transcriptase (hTERT)-RPE cells was examined by reverse transcription polymerase chain reaction (RT-PCR) and Northern blot analysis. Carrier-mediated ornithine transport via the L-type amino acid transporter (LAT)1, LAT2, cationic amino acid transporter (CAT)-1, and y(+)LAT2 systems was evaluated by short interfering (si)RNA-mediated gene silencing. The cytoprotective effect of CAT-1-specific siRNA on ornithine cytotoxicity was measured using quantitative analysis of cellular adenosine triphosphate (ATP) at 24 hours after treatment with ornithine in OAT-deficient RPE cells. RESULTS: LAT1, LAT2, CAT-1, and y(+)LAT2 mRNA expression was detected by Northern blot analysis, whereas RT-PCR revealed that LAT1, LAT2, y(+)LAT1, y(+)LAT2, CAT-1, and b(0,+)AT mRNAs were expressed together with the heterodimeric glycoproteins 4F2hc and rBAT in hTERT-RPE cells. l-[(14)C]ornithine uptake in hTERT-RPE cells was decreased by 46.6% and 22.0% by CAT-1 and y(+)LAT2 siRNA, respectively, whereas LAT1 and LAT2 siRNA had no significant effect. Further, CAT-1 silencing by siRNA reduced ornithine cytotoxicity in OAT-deficient RPE cells. CONCLUSIONS: The results suggest that ornithine transport via CAT-1 may play a crucial role in ornithine cytotoxicity in hTERT-RPE cells. Reduction of the ornithine transport via CAT-1 may be a new target for treatment of gyrate atrophy.

Adenosine Triphosphate↗

PubMed2006

Pars plana vitrectomy with removal of posterior hyaloid face in treatment of refractory diabetic macular edema resistant to triamcinolone acetonide.

BACKGROUND: Triamcinolone acetonide (TA) has recently been used to treat diabetic macular edema (DME) but its effectiveness is limited. CASES: Three patients (three eyes) with unresolved diffuse DME who did not respond to a posterior sub-Tenon's injection of TA underwent vitrectomy. OBSERVATIONS: Intraoperatively, it was found that all of the eyes had a posterior hyaloid face that was adherent to a large area of the posterior pole retina, although this had not been detected by slit-lamp biomicroscopy or optical coherence tomography. After vitrectomy and removal of the posterior hyaloid face, there was a significant reduction in the central macular thickness of all three eyes and an improvement in the visual acuity of the patients. CONCLUSIONS: When TA treatment is not effective for DME, vitrectomy with the complete removal of the posterior hyaloid face, including removal of the internal limiting membrane, should be considered.

Aged↗

PubMed2006

Poly (ADP-ribose) polymerase inhibitor 3-aminobenzamide rescues N-methyl-N-nitrosourea-induced photoreceptor cell apoptosis in Sprague-Dawley rats through preservation of nuclear factor-kappaB activity.

The activation of poly (ADP-ribose) polymerase (PARP) plays a pivotal role in mediating N-methyl-N-nitrosourea (MNU)-induced photoreceptor cell apoptosis. We examined the retinoprotective effects of the PARP inhibitor 3-aminobenzamide (3-AB) against MNU-induced retinal damage in relation to dose and timing of prescription, and the involvement of the transcription factor nuclear factor (NF)-kappaB. Female Sprague-Dawley rats were intraperitoneally injected with 60 mg/kg MNU at 50 days of age, and were then immediately given a subcutaneous injection of 0, 1, 5, 10, 30 or 50 mg/kg of 3-AB, or were injected with 50 mg/kg 3-AB 12h before, concurrently, or 4, 6 or 12h after MNU. Rats were killed 3 and 7 days after MNU, and MNU-treated and 3-AB-injected retinas were compared with MNU-untreated control retinas or MNU-treated/3-AB-uninjected retinas. Apoptosis in photoreceptor cells was detected by performing formamide-induced DNA denaturation and staining with anti-single-stranded DNA antibody. Retinal morphologies were compared and evaluated morphometrically using the photoreceptor cell ratio and retinal damage ratio as indices to evaluate the efficacy of 3-AB. We examined expression of the phosphorylated form of NF-kappaB and IkappaBalpha (p-NF-kappaB and p-IkappaBalpha, respectively) in retinas of MNU-treated rats concurrently treated with or without 50mg/kg 3-AB, compared with MNU-untreated control retinas. 3-AB dose-dependently suppressed photoreceptor cell apoptosis: 50mg/kg 3-AB injected concurrently with MNU completely rescued photoreceptor cell damage; 30 mg/kg 3-AB significantly reduced photoreceptor cell damage; 10 mg/kg 3-AB tended to suppress photoreceptor cell damage; or=4h after MNU, it did not exert a retinoprotective effect. p-NF-kappaB levels of MNU-treated rat retinas were significantly lower than those of MNU-untreated control retinas, while 50 mg/kg 3-AB injected concurrently with MNU preserved the p-NF-kappaB levels; p-IkappaBalpha levels tended to decrease after MNU injection, compared with untreated control retinas, but the difference was not significant. Thus, 3-AB dose-dependently suppressed MNU-induced retinal damage, and 50mg/kg 3-AB injected concurrently with MNU completely rescued photoreceptor cell apoptosis via preservation of NF-kappaB activity.

Animals↗

PubMed2006

Elevation of monocyte-derived microparticles in patients with diabetic retinopathy.

Diabetic retinopathy is associated with microvascular damage and capillary occlusions which are common features of the microangiopathy in diabetes. Monocyte-derived microparticles (MDMPs) are released from activated monocytes and enhance the procoagulant activity, and also activate adhesion reactions. These are key events in the development of capillary occlusion. The MDMPs level in the blood, and platelet activation markers (platelet-derived microparticles (PDMPs), CD62P and CD63) were measured by flow cytometry in 72 diabetic patients. The plasma levels of intracellular adhesion molecule-1 (ICAM-1) and P-selectin were analyzed by ELISA. The level of MDMPs was significantly correlated with the levels of PDMPs (r=0.52, P<0.001), CD62P (r=0.37, P=0.001), CD63 (r=0.31 and P=0.007), P-selectin (r=0.38, P=0.001), and ICAM-1 (r=0.31, P=0.009). The MDMPs level increased with the progression of the diabetic retinopathy: 81+/-14/10(4)platelets (plts) in patients without retinopathy (n=10); 88+/-8/10(4)plts with mild or moderate non-proliferative diabetic retinopathy (NPDR, n=12); 95+/-8/10(4)plts with severe NPDR (n=24); and 112+/-9/10(4)plts with proliferative diabetic retinopathy (PDR) (n=26). The MDMPs level in patients with areas of capillary occlusion (123+/-10/10(4)plts, n=25) was significantly higher than that in patients without areas of capillary occlusion (84+/-5/10(4)plts, n=25; P=0.0008). These correlations suggest that increased levels of MDMPs may accelerate the progression of diabetic retinopathy.

Adult↗

PubMed2006

[Bacterial endopathalmitis caused by B streptococcus endocarditis].

BACKGROUND: Bacterial endophthalmitis is often caused by a shift in the primary focus of infection in the patient's body. It is a high risk disease that can cause the loss of sight. Bacterial endophthalmitis with infectious endocarditis is very rare in Japan. CASE: A fifty-three-year-old woman visited our clinic complaining of pain, fever, and visual impairment in her left eye. OBSERVATIONS: The patient's left eye was blind, and showed hapopyon in the anterior chamber. She was admitted to our hospital with a diagnosis of endophthalmitis. Medical treatment with antibiotics was carried out, but the inflammation in her left eye increased. Her left eye was enucleated, and group B Streptococcus was found in the vitreous specimen. Echocardiography demonstrated vegetation of the posterior mitral valve. The diagnosis was made of endophthalmitis due to infectious endocarditis. CONCLUSION: We report an endophthalmitis patient with infectious endocarditis caused by group B streptococcus, based on histopathological findings. This is the first such case reported in Japan.

Endocarditis, Bacterial↗

PubMed2006

[Optical coherence tomographic findings of the retinal pigment epithelium tear in macular area preserving good visual acuity].

PURPOSE: It has been reported that the visual outcome of retinal pigment epithelial tear (RPE tear) in the fovea is worse than that of RPE tear sparing the fovea. We report optical coherence tomography (OCT) findings of 3 cases with RPE tear in the fovea who preserved good visual acuity. PATIENTS: All patients had serous retinal pigment epithelial detachment involving the macula. The RPE was torn and rolled RPE was observed in the fovea. In OCT findings, a fovea was observed on the RPE flap, and visual acuity was preserved after RPE tear repair. CONCLUSION: We considered that preservation of good visual acuity was due to the presence of a fovea on the RPE flap. We could precisely analyze the location of the fovea and RPE tear using OCT.

Aged↗

PubMed2006

[Evaluation of cases of polypoidal choroidal vasculopathy showing classic choroidal neovascularization in their natural course].

BACKGROUND: Some cases of polypoidal choroidal vasculopathy (PCV) in their natural course develop into classic choroidal neovascularization(CNV) as shown by fluorescein angiography (FA) findings. SUBJECTS AND METHOD: We evaluated 8 eyes of 8 PCV patients showing classic CNV by FA findings, using indocyanine green angiography (IA) and optical coherence tomography(OCT). RESULT: All patients showed subretinal grayish exudates, which were considered fibrinous. Five cases were recognized as true subretinal CNV according to IA and OCT findings. The other 3 patients showed polypoidal dilatation with vascular networks by IA, and a moderately reflective mass considered fibrinous over the polypoidal elevation of retinal pigment epithelium (RPE) by OCT. CONCLUSION: Both true CNV and PCV with fibrin are present in PCV patients showing classic CNV. It requires care to determine proper treatment.

Aged↗

PubMed2005

Long-term survival of bone marrow-derived retinal nerve cells in the retina.

Recently, we have demonstrated that bone marrow stem cells can differentiate into retinal nerve cells. In the present study, we show a new and efficient strategy for transplanting bone marrow stem cells into the retina. When bone marrow stem cells were injected into the vitreous cavity of untreated eyes, only very few cells were found in the retina 2 weeks after injection. In contrast, when laser photocoagulation was performed just before the injection of bone marrow stem cells, a large number of the injected cells survived 2 weeks after injection and the cells expressed neural cell-specific or retinal nerve cell-specific antigens. Moreover, we still detected bone marrow stem cell-derived retinal nerve cells in the retina 1 year after injection in the retina.

Analysis of Variance↗

PubMed2005

High levels of pigment epithelium-derived factor in the retina of a rat model of type 2 diabetes.

Spontaneously diabetic Torii (SDT) rats are a new animal model of diabetes. To investigate the mechanisms controlling diabetic retinopathy, we examined the retinal changes in SDT rats and determined the molecular balance between pigment epithelium-derived factor (PEDF), an angiogenic inhibitor, and vascular endothelial growth factor (VEGF), a major angiogenic stimulator. The retinopathy in SDT rats was characterized by a low incidence of neovascular formation and absence of non-perfused areas, and high levels of both PEDF and VEGF. Proliferative neovascular membranes, that are similar to that in human eyes with proliferative diabetic retinopathy, were found in the eyes of some of the SDT rats at >50-weeks-of-age, Immunoreactivity for VEGF was detected in the retina of SDT rats and the level of VEGF increased with the duration of diabetes. More importantly, immunoreactivity for PEDF was also increased in the retina of diabetic SDT rats. Western blot analysis showed that the level of VEGF in the retina was increased by 2.4 fold at 20-week-old, and by 6.8 fold at >40-week-old compared to that of 10-weeks old SDT rats. The levels of PEDF in the retina at 20-week- and at >40-week-old were significantly higher than that of 10-weeks old SDT rats (20-week-old; 13.5-fold increase, > 40-week-old; 10.3-fold increase). Earlier studies showed that the level of PEDF was decreased and VEGF was increased in proliferative diabetic retinopathy in human eyes. The high levels of PEDF in the retina of SDT rats may contribute to the low incidence of neovascular formation and absence of non-perfused areas that do not match the typical diabetic retinopathy in humans.

Animals↗

PubMed2005

Bilateral orbital tumor as initial presenting sign in human T-cell leukemia virus-1 associated adult T-cell leukemia/lymphoma.

PURPOSE: To report a case of human T-cell leukemia virus type1 (HTLV-1)-associated adult T-cell leukemia/lymphoma (ATLL) whose initial sign was exophthalmos. DESIGN: Case report. METHODS: A 64-year-old Japanese man presented with exophthalmos and choroidal folds of the right eye without general symptoms and received ophthalmologic and laboratory examination, magnetic resonance imaging (MRI), and orbital biopsy. RESULTS: Antibodies against HTLV-1 were extremely high but atypical lymphocytes were not present in the peripheral blood. MRI showed multiple tumorous lesions in both orbits. Orbital biopsy revealed an orbital mass that consisted of atypical lymphocytes originally from T cells and established the diagnosis of lymphoadenopathy type of ATLL. CONCLUSION: Although ocular involvement by ATLL is extremely rare, ATLL can first present in the orbit, and only the results of a biopsy can provide definitive information for its diagnosis.

Antibodies, Viral↗

PubMed2005

Low levels of pigment epithelium-derived factor in highly myopic eyes with chorioretinal atrophy.

PURPOSE: To determine the concentration of pigment epithelium-derived factor (PEDF) in the aqueous humor of highly myopic eyes. DESIGN: Observational case series. METHODS: The PEDF concentration in the aqueous humor of 23 eyes of 17 patients with high myopia (axial length >26 mm) who underwent cataract surgery was measured by enzyme-linked immunosorbent assay. RESULTS: The mean concentration of PEDF in eyes with high myopia (0.54 +/- 0.12 microg/ml) was significantly lower than that in control eyes (0.86 +/- 0.04 microg/ml, P = .0022). The PEDF level in myopic eyes with chorioretinal atrophy (0.32 +/- 0.05 microg/ml) was lower than that in myopic eyes without chorioretinal atrophy (0.71 +/- 0.12 microg/ml; P = .041) and control eyes (P = .0003). CONCLUSIONS: The significantly lower concentration of PEDF in eyes with chorioretinal atrophy-associated high myopia probably resulted from degeneration of the retinal pigment epithelial cells and/or the retinal ganglion cells that are the main sources of PEDF in the eye.

Aged↗

PubMed2005

Cytoprotection by nipradilol, an anti-glaucomatous agent, via down-regulation of apoptosis related gene expression and activation of NF-kappaB.

It has been reported that nipradilol, a nonselective beta- and selective alpha1-receptor antagonist, has cytoprotective effects. We attempted to clarify the effects of nipradilol on the expression of apoptosis associated genes and the activity of nuclear factor-kappaB, a transcription factor, in PC12 cells during serum deprivation induced apoptosis. PC12 cells were cultured in serum free RPMI1640 medium with or without 0.01, 0.1, 1, or 10 microM of nipradilol, or in serum-added medium as a control. The gene expressions of Bax, Bcl-2, Fas, FasL, Caspase-1, 2, 3, and 9, p53, and Smac/DIABLO were examined using a quantitative real time polymerase chain reaction method, while nuclear factor-kappaB activity was examined using an electrophoresis mobility shift assay with a nuclear factor-kappaB consensus sequenced DNA probe. The effects of denitronipradilol were also examined to clarify the effect of nitric oxide donative action. Nipradilol down-regulated Bax gene expression 12 hr after serum deprivation, and that of the capase-9 and Smac/DIABLO genes at 24 hr, compared to the serum-free sample, while it also increased cell viability and decreased DNA ladder formation at 48 hr. However, the expressions of other examined genes were not affected by the agent. In addition, nuclear factor-kappaB activity was increased 2 hr after the addition of 0.1 or 1 microM of nipradilol. In contrast, denitronipradilol did not show any effects toward PC12 cells. Our results suggest that nipradilol may have an effect on apoptosis associated gene expression and nuclear factor-kappaB activity during the prevention of apoptosis via nitric oxide donative action.

Adrenergic alpha-Antagonists↗

PubMed2005

Autopsy case of primary choriocarcinoma of the urinary bladder.

Choriocarcinomas usually develop in the uterus and ovaries in the female, being extremely rare in the extragenital organs in the male. Extragenital choriocarcinomas in the male usually develop in the mediastinum or retroperitoneum. The frequency of choriocarcinoma in the urinary bladder is extremely low. The purpose of the present paper was to report an autopsy case of choriocarcinoma in the urinary bladder in the male. An 81-year-old male patient with macrohematuria was first diagnosed with transitional cell carcinoma (TCC). At autopsy a hemorrhagic necrotic tumor, which was found in the urinary bladder with metastatic lesions in the lungs, was diagnosed as choriocarcinoma microscopically. There was no evidence for choriocarcinoma derived from any other organs than the urinary bladder, although there were metastatic lesions in both lungs and the direct invasion into the prostate. From these findings it is concluded that the tumor was a primary choriocarcinoma in the urinary bladder in a male patient. Choriocarcinoma of the urinary bladder is very rare, but the prognosis is extremely poor in comparison with TCC even in the urinary bladder. Therefore, it is essential to clearly discriminate between choriocarcinomas and TCC.

Aged↗

PubMed2005

Macrophage colony-stimulating factor (M-CSF), as well as granulocyte colony-stimulating factor (G-CSF), accelerates neovascularization.

It has been reported that bone marrow cells (BMCs) differentiate into endothelial cells of blood vessels, and that granulocyte colony-stimulating factor (G-CSF) mobilizes progenitors in the BMCs to the peripheral blood, while macrophage colony-stimulating factor (M-CSF) augments the production of monocytes. We examined whether M-CSF augments the differentiation of BMCs into endothelial cells of blood vessels using a hindlimb-ischemic model. Either G-CSF or M-CSF, or both, was administered to the hindlimb-ischemic mice for 3 days. Both M-CSF and G-CSF augmented the differentiation of BMCs into endothelial cells of blood vessels through vascular endothelial cell growth factor (VEGF), resulting in early recovery of blood flow in the ischemic limbs.

Animals↗

PubMed2005

[Vitrectomy for proliferative diabetic retinopathy].

PURPOSE: We reviewed the outcome of vitrectomy for proliferative diabetic retinopathy (DR) and evaluated factors affecting the final visual outcome. METHODS: We performed primary vitreous surgery for proliferative DR in 148 eyes of 118 cases in three years from July 1999 to August 2002. All cases were followed for at least 3 months. We excluded vitreous surgery for diabetic maculopathy. Ages ranged from 24 to 80 (mean 57) years. Average postoperative follow-up period was 15 months. We evaluated the stage of DR by the new Fukuda classification. RESULT: Preoperative classification consisted of BIV (54 eyes, 36%), BV (94 eyes, 64%), and BV + VI (36 eyes). Final visual acuity was improved by 2 lines or more in 102 eyes (69%), remained unchanged in 28 eyes (19%), and decreased by two lines or more in 18 eyes (12%). There was a statistical correlation between preoperative visual acuity and final visual acuity. Earlier stages of DR had better visual outcome. Compared to the surgical outcome in the 1990s, the percentage of worsened eyes decreased. CONCLUSION: Vitrectomy for proliferative DR may be beneficial if performed in the earlier stages of DR or if the patient has better visual acuity before vitrectomy.

Adult↗