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Nahoko Ogata

Publications and source records attributed to Nahoko Ogata.

13 recordsLinked to original sources
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↗
PubMed2004

Increased levels of platelet-derived microparticles in patients with diabetic retinopathy.

Diabetic retinopathy is caused by capillary occlusions. Platelet-derived microparticles (PMPs) stimulate the coagulation cascade and increase leukocyte and endothelial cell adhesions, both of which are key events in the development of diabetic retinopathy. However, the correlation between the levels of PMPs and diabetic retinopathy has not been precisely determined. The PMPs levels and the expression of platelet CD62P and CD63 were measured in 92 diabetic patients. The level of PMPs was significantly correlated with the expression of CD62P (r = 0.76, P < 0.0001) and CD63 (r = 0.71, P < 0.0001). The mean level of PMPs in diabetics (507+/-15/10(4) platelets (plt), mean+/-S.E.) was significantly higher than that in normal. The PMPs levels increased with the progression of the diabetic retinopathy; 480+/-28/10(4) plt in diabetic patients without retinopathy (n = 25), 504+/-40/10(4) plt with mild or moderate non-proliferative diabetic retinopathy (n = 13), 512+/-29/10(4) plt with severe non-proliferative diabetic retinopathy (n = 25), and 528+/-25/10(4) plt with proliferative diabetic retinopathy (n=29). The PMPs level in patients with non-perfused retinal areas (582+/-27/10(4) plt, n = 24) was significantly higher than patients without non-perfused areas (469+/-23/10(4) plt, n = 30; P = 0.0096) and without diabetic retinopathy (P = 0.024). These high correlations indicate that increased levels of PMPs may accelerate diabetic retinopathy.

Adult↗
PubMed2004

In vivo evidence of angiogenesis induced by transcription factor Ets-1: Ets-1 is located upstream of angiogenesis cascade.

BACKGROUND: A transcription factor, ets-1, regulates the transcription of metalloproteinase genes, the activity of which is necessary for matrix degradation and the migration of endothelial cells. However, no study has demonstrated that ets-1 itself has an angiogenic action in vivo. Thus, we examined (1) the effects of overexpression of the ets-1 gene on angiogenesis in a rat hindlimb ischemia model, and (2) how ets-1 induced angiogenesis. METHODS AND RESULTS: In this study, we used the HVJ-liposome method, which is highly effective for transfection, to transfect the human ets-1 gene. At 4 weeks after transfection, the capillary density and blood flow were significantly increased in a hindlimb transfected with the human ets-1 gene compared with control. These data clearly demonstrated that ets-1 has the ability to stimulate angiogenesis in vivo. To elucidate the molecular mechanisms by which ets-1 induced angiogenesis, we focused especially on the expression of hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF), potent angiogenic growth factors, because the promoter regions of both genes contain ets binding sites. Interestingly, overexpression of ets-1 upregulated both tissue HGF and VEGF concentrations in rat hindlimb. More importantly, administration of neutralizing antibody against HGF and VEGF attenuated the increase in blood flow and BrdU-positive cells induced by ets-1. Upregulation of HGF and VEGF by ets-1 was also confirmed by in vitro experiments using human vascular smooth muscle cells. CONCLUSIONS: The present study demonstrated that ets-1 regulated angiogenesis through the induction of angiogenic growth factors (VEGF and HGF). Overexpression of ets may provide a new therapeutic strategy to treat peripheral arterial disease.

Animals↗
PubMed2004

Decrease of pigment epithelium-derived factor in aqueous humor with increasing age.

PURPOSE: To determine whether the level of pigment epithelium-derived factor (PEDF) in the aqueous humor is altered with age. DESIGN: Observational case series. METHODS: The PEDF concentration in the aqueous humor was measured by enzyme-linked immunosorbent assay in 152 eyes of 121 patients who underwent cataract surgery. RESULTS: The mean aqueous level of PEDF was 0.86 +/- 0.04 microg/ml (mean +/- standard error, 70.7 +/- 1.0 years). The PEDF levels decreased with increasing age, and the decrease was significantly correlated with age (Pearson product moment correlation coefficient, r = - 0.22, P =.006). The mean PEDF level in the men (0.76 +/- 0.06 microg/ml, 53 eyes, 71.5 +/- 2.0 years) was significantly lower than that in women (0.91 +/- 0.04 microg/ml, 99 eyes, 70.2 +/- 1.1 year, P =.03). CONCLUSIONS: The negative correlation of PEDF level and age should be considered in age-related eye diseases, especially those associated with angiogenesis.

Adolescent↗
PubMed2004

Decreased levels of pigment epithelium-derived factor in eyes with neuroretinal dystrophic diseases.

PURPOSE: To determine the concentration of pigment epithelium-derived factor (PEDF) in the aqueous humor of eyes with neuroretinal dystrophy. DESIGN: Observational case series. METHODS: Aqueous humor was obtained from patients during cataract surgery, and the PEDF concentration in the aqueous humor was measured by enzyme-linked immunosorbent assay. The primary diagnosis was cataract in 162 eyes; of these there were five eyes with retinitis pigmentosa, nine eyes with advanced glaucoma, and 148 eyes with cataract alone. RESULTS: The mean levels of PEDF in eyes with retinitis pigmentosa (0.24 +/- 0.04 microg/ml, mean +/- SE, P =.0004) and advanced glaucoma (0.46 +/- 0.08 microg/ml, P =.003) were significantly lower than that in eyes with cataract alone (0.86 +/- 0.04 microg/ml). CONCLUSION: The lower levels of PEDF in eyes with neuroretinal dystrophy may be related to the loss of the retinal ganglion cells or retinal pigment epithelium cells that synthesize PEDF.

Aged↗
PubMed2002

Inverse levels of pigment epithelium-derived factor and vascular endothelial growth factor in the vitreous of eyes with rhegmatogenous retinal detachment and proliferative vitreoretinopathy.

PURPOSE: To determine the vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor in eyes with rhegmatogenous retinal detachment and proliferative vitreoretinopathy. DESIGN: Prospective, noncomparative case series. METHODS: Pigment epithelium-derived factor and vascular endothelial growth factor concentrations were measured by enzyme-linked immunosorbent assay in 26 eyes with retinal detachment, 6 with proliferative vitreoretinopathy, and 14 with an idiopathic macular hole. RESULTS: Pigment epithelium-derived factor concentration in proliferative vitreoretinopathy (0.57 +/- 0.05 microg/ml) was lower (P =.0069), and retinal detachment (2.37 +/- 0.34 microg/ml) was higher (P =.16) than that in macular hole (1.71 +/- 0.22 microg/ml). Vascular endothelial growth factor concentration (168 +/- 139 microg/ml) in proliferative vitreoretinopathy was significantly higher than that in retinal detachment (11 +/- 11 microg/ml, P =.0084) and macular hole (not detectable, P =.0095). CONCLUSION: Lower levels of pigment epithelium-derived factor and higher levels of vascular endothelial growth factor may be related to ocular cell proliferation.

Endothelial Growth Factors↗
PubMed2002

Unbalanced vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor in diabetic retinopathy.

PURPOSE: To determine the levels of pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) in the vitreous of patients with diabetic retinopathy (DR). DESIGN: Experimental study of PEDF and VEGF levels in vitreous samples collected during vitrectomy. METHODS: The levels of PEDF and VEGF were measured by enzyme-linked immunosorbent assay in the vitreous of 46 eyes of 43 patients who underwent vitrectomy with diabetic retinopathy (DR) (32 eyes of 29 patients) and an idiopathic macular hole (MH) (14 eyes of 14 patients). RESULTS: The vitreal concentration of PEDF was significantly lower at 1.11 +/- 0.14 microg/ml (mean +/- standard error) in eyes with DR than in eyes with MH at 1.71 +/- 0.22 microg/ml (P =.021). The VEGF level was 1799 +/- 478 pg/ml in eyes with DR and not detectable in MH. The PEDF level in proliferative DR (PDR) (0.94 +/- 0.12 microg/ml) was lower than that in nonproliferative DR (NPDR) (2.25 +/- 0.32 microg/ml), and that in active DR (0.85 +/- 0.14 microg/ml) was significantly lower than that in inactive DR (1.59 +/- 0.24 microg/ml; P =.01). The VEGF level was 2025 +/- 533 pg/ml in PDR and 215 +/- 201 pg/ml in NPDR and that in active DR (2543 +/- 673 pg/ml) was significantly higher than that in inactive DR (395 +/- 188 pg/ml; P =.0098). CONCLUSIONS: These results suggest that lower levels of PEDF and higher levels of VEGF may be related to the angiogenesis in DR that leads to active PDR.

Adult↗
PubMed2002

Effective transfection of a cis element "decoy" of the nuclear factor-kappaB binding site into the experimental choroidal neovascularization.

PURPOSE: To evaluate the efficacy of the gene transfer of a double-stranded phosphorothioate oligonucleotides (ODNs), called a "decoy", against the NF-kappaB binding site into cells of an experimentally-induced choroidal neovascularization. METHODS: FITC-labeled decoy was injected into the subretinal space of rat eyes by the HVJ-liposome delivery system, and 3 days later, choroidal neovascularization was induced by laser photocoagulation. The eyes were removed and the transfected cells were detected by fluorescence microscopy and also detected by immunohistochemistry. The degree of neovascularization was evaluated by fluorescein angiography. RESULTS: The decoy was transfected into the retinal pigment epithelial (RPE) cells, inner and outer segment of the photoreceptors at 3 days after the injection. When choroidal neovascularization was induced, highly effective transfection of the decoy was observed 3 to 14 days after photocoagulation, after which the level decreased. Decoys were transfected into the RPE cells and macrophages in the choroidal neovascularization. The eyes transfected with NF-kappaB decoy showed a weaker leakage in fluorescein angiograms than that of the control eyes transfected with scrambled decoy. CONCLUSIONS: A decoy can be transfected into retinal cells and cells within a choroidal neovascularization by the HVJ-liposome method. The transferred NF-kappaB decoy reduced the degree of choroidal neovascularization. Decoy targeted against NF-kappaB may be considered as a potential therapy for neovascularization.

Animals↗
PubMed2002

Expression of pigment epithelium-derived factor in normal adult rat eye and experimental choroidal neovascularization.

PURPOSE: Pigment epithelium-derived factor (PEDF) is a protein produced by the retinal pigment epithelial (RPE) cells. Recent studies have implicated PEDF in activities that are inhibitory to angiogenesis. In this study, the expression of PEDF was investigated in normal rat eyes and in eyes with experimentally induced choroidal neovascularization and compared with the expression of vascular endothelial growth factor (VEGF). METHODS: Choroidal neovascularization was induced by laser photocoagulation in rat eyes. At intervals of up to 2 weeks after photocoagulation, the eyes were removed and prepared for in situ hybridization and immunohistochemical study. In situ hybridization was performed with digoxigenin-labeled PEDF riboprobes. Protein expression of PEDF and VEGF was studied immunohistochemically. RESULTS: In normal adult rat eyes, PEDF mRNA was observed mainly in the corneal epithelial and endothelial cells, lens epithelial cells, ciliary epithelial cells, retinal ganglion cells, and the RPE cells. During the development of choroidal neovascularization, PEDF mRNA, PEDF protein, and VEGF protein were strongly detected in many cells within the laser lesions at 3 days after photocoagulation, after which levels gradually declined. However, PEDF was still expressed in the RPE cells that proliferated and covered the neovascular tissues at 2 weeks, whereas VEGF protein was weakly expressed in endothelial cells in choroidal neovascularization. CONCLUSIONS: PEDF is expressed in different cell types of normal rat eyes. The expression of PEDF was detected in the choroidal neovascular tissues induced by photocoagulation, and these findings suggest that PEDF may modulate the process of choroidal neovascularization.

Animals↗
PubMedDate not supplied

Expression of transforming growth factor-beta receptors in normal rat retina and experimental choroidal neovascularization.

PURPOSE: Transforming growth factor-beta (TGF-beta) plays an important role in the development of choroidal neovascularization. TGF-beta transduces signals through the mediation of type I and type II receptors. We investigated the expression of TGF-beta receptors in a normal rat retina and a model of experimentally induced choroidal neovascularization. METHODS: Choroidal neovascularization was induced by laser photocoagulation in rat eyes. The expression of TGF-beta receptors was determined using immunohistochemical and in situ hybridization methods. RESULTS: In normal adult rat retinas, immunoreactivity and mRNA expression of TGF-beta receptor type I (TbetaRI) and TGF-beta receptor type II (TbetaRII) were found in the ganglion cells. During the process of neovascularization, immunoreactivity and mRNA expression of TbetaRI and TbetaRII were widely distributed in laser lesions soon after photocoagulation; thereafter, these receptors were specifically detected in the endothelial cells of choroidal neovascularization. CONCLUSIONS: The expression of TGF-beta receptors in normal rat retinas suggests that TGF-beta plays an important role in the homeostasis of normal retina. The upregulation of TGF-beta receptors in choroidal neovascularization strongly suggests that TGF-beta is most likely transduced through specific receptors and plays an important role in the development of choroidal neovascularization.

Animals↗