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Yoshihisa Oguchi

Publications and source records attributed to Yoshihisa Oguchi.

At least 37 records · Page 2Linked to original sources
PubMed2004

[Intravitreal injection of triamcinolone acetonide for cystoid macular edema resistant to vitreous surgery].

PURPOSE: To report the efficacy of intravitreal injection of triamcinolone acetonide(TA) for cystoid macular edema remaining after vitreous surgery. METHODS: Eight eyes of 7 patients aged from 32 to 84 years old were studied. The original diseases that caused macular edema were central retinal vein occlusion in 2 eyes, branch retinal vein occlusion in one eye, Irvine-Gass syndrome in 2 eyes, and diabetic retinopathy in 3 eyes. 4 mg of TA was injected intravitreally and visual acuity and foveal thickness measured by optical coherence tomography(OCT) were evaluated in before and after the surgery. RESULTS: Macular edema resolved rapidly after injection of TA in all cases and cysts were extinguished or diminished. The foveal thickness in OCT was reduced significantly from preoperative 495 +/- 116 (mean +/- standard deviation) microns to 267 +/- 117 microns after one week, and 246 +/- 81 microns after one month. The effect persisted for three months. Visual improvement of more than two Snellen lines was seen in 4 eyes. No side effects were observed except a temporary increase of intraocular pressure in one eye. CONCLUSION: Intravitreal injection of TA is effective in a short-term for cystoid macular edema remaining after vitrectomy.

Adult↗
PubMed2004

[Significance of leukocytes in the regulation of retinal edema, ischemia, and angiogenesis].

BACKGROUND: Involvement of leukocytes in three major pathologic conditions in the retina, i.e., edema, ischemia, and angiogenesis, has recently been thoroughly investigated. The accumulated evidence will lead to an integrated understanding of the relationship between leukocytes and retinal disorders, which is required for clinical applications of new medical treatment. METHOD: Leukocyte roles in the retinal vascular pathology were assessed by reviewing the related literature. RESULTS: Vascular endothelial growth factor(VEGF)-induced leukocyte adhesion to the retinal vessels was shown to result in blood-retinal barrier breakdown, and the leukocyte-mediated pathogenesis was also seen in a model of diabetic retinopathy. A possible mechanism by which retinal angiogenesis develops intraviteral proliferation instead of compensating the avascular retina is that VEGF-producing monocytes/macrophages infiltrate the vitreous with subsequent migration of retinal vascular endothelial cells. On the other hand, cytotoxic T lymphocyte-mediated apoptosis of endothelial cells appears to cause the suppression of pathological retinal angiogenesis and the formation of ischemic retina secondary to vascular regression. CONCLUSION: Leukocytes are considered to regulate retinal edema, ischemia, and angiogenesis.

Animals↗
PubMed2004

[Genetic diagnosis of retinoblastoma by a combination of fluorescence in situ hybridization and restriction fragment length polymorphism].

PURPOSE: It is important to exclude germ line mutation in cases of unilateral retinoblastoma(RB) to estimate hereditary or possible secondary cancer. We investigated whether genetic diagnosis is feasible in a health check screening program. METHODS: Five patients with RB had surgery for enucleation in Keio University Hospital. Tumor cells from enucleated eyes and lymphocytes representing systemic cells were collected and analyzed genetically by fluorescence in situ hybridization(FISH) and restriction fragment length polymorphism (RFLP). RESULTS: One out of three unilateral RB cases could be diagnosed as non-hereditary by the finding of no copies of the RB gene in the tumor cells using the FISH method and no signal in the RFLP method. A decrease of signal in tumor cells to less than 50% in the RFLP method was observed in another case of unilateral RB that seemed to be non-hereditary, but the case ultimately could not be diagnosed as non-hereditary because polycopies were found in the FISH method. No abnormality in tumor cells could be found in another unilateral case or in systemic cells of two bilateral cases. CONCLUSION: A combination of FISH and RFLP methods can be used to diagnose some cases of RB as non-hereditary.

Child, Preschool↗
PubMed2003

Characterization of AOC2 gene encoding a copper-binding amine oxidase expressed specifically in retina.

We have previously cloned a human, retina-specific, amine oxidase gene (RAO, gene symbol: AOC2), a member of the copper-binding amine oxidase super family. AOC2 shares sequence identity with the human kidney amine oxidase gene (KAO, gene symbol: AOC1) and the vascular adhesion protein-1 gene (VAP-1, gene symbol: AOC3). For further analysis of AOC2, the sequences surrounding the human AOC2 and the complete mouse and partial rat homologue of AOC2 were cloned for characterization. Real-time quantitative PCR, in situ hybridization, and immunohistochemistry were performed to determine the specific expression of AOC2 in the mouse retina and especially in the retinal ganglion cells. Our results demonstrated that the copper-binding motif and the enzyme active site of AOC1 and AOC3 were both conserved in mouse AOC2. The human and mouse AOC2 was flanked by two genes, the Psme3 gene for PA-28 gamma subunit and, surprisingly, the AOC3 gene. Rat AOC2 contained a stop codon that terminated the peptide length to 127 amino acids. The presence of human and rat AOC pseudogene in this region, in addition to the tandemly positioned two AOC genes, indicates the possibility of successful AOC3 replication to retina-specific AOC2 for human and mouse but unsuccessful for rat.

Amine Oxidase (Copper-Containing)↗
PubMed2003

VEGF164-mediated inflammation is required for pathological, but not physiological, ischemia-induced retinal neovascularization.

Hypoxia-induced VEGF governs both physiological retinal vascular development and pathological retinal neovascularization. In the current paper, the mechanisms of physiological and pathological neovascularization are compared and contrasted. During pathological neovascularization, both the absolute and relative expression levels for VEGF164 increased to a greater degree than during physiological neovascularization. Furthermore, extensive leukocyte adhesion was observed at the leading edge of pathological, but not physiological, neovascularization. When a VEGF164-specific neutralizing aptamer was administered, it potently suppressed the leukocyte adhesion and pathological neovascularization, whereas it had little or no effect on physiological neovascularization. In parallel experiments, genetically altered VEGF164-deficient (VEGF120/188) mice exhibited no difference in physiological neovascularization when compared with wild-type (VEGF+/+) controls. In contrast, administration of a VEGFR-1/Fc fusion protein, which blocks all VEGF isoforms, led to significant suppression of both pathological and physiological neovascularization. In addition, the targeted inactivation of monocyte lineage cells with clodronate-liposomes led to the suppression of pathological neovascularization. Conversely, the blockade of T lymphocyte-mediated immune responses with an anti-CD2 antibody exacerbated pathological neovascularization. These data highlight important molecular and cellular differences between physiological and pathological retinal neovascularization. During pathological neovascularization, VEGF164 selectively induces inflammation and cellular immunity. These processes provide positive and negative angiogenic regulation, respectively. Together, new therapeutic approaches for selectively targeting pathological, but not physiological, retinal neovascularization are outlined.

Animals↗
PubMed2003

Leukocytes mediate retinal vascular remodeling during development and vaso-obliteration in disease.

Retinal ischemia can cause vision-threatening pathological neovascularization. The mechanisms of retinal ischemia are not fully understood, however. Here we have shown that leukocytes prune the retinal vasculature during normal development and obliterate it in disease. Beginning at postnatal day 5 (P5) in the normal rat, vascular pruning began centrally and extended peripherally, leaving behind a less dense, smaller-caliber vasculature. The pruning was correlated with retinal vascular expression of intercellular adhesion molecule-1 (ICAM-1) and coincided with an outward-moving wave of adherent leukocytes composed in part of cytotoxic T lymphocytes. The leukocytes adhered to the vasculature through CD18 and remodeled it through Fas ligand (FasL)-mediated endothelial cell apoptosis. In a model of oxygen-induced ischemic retinopathy, this process was exaggerated. Leukocytes used CD18 and FasL to obliterate the retinal vasculature, leaving behind large areas of ischemic retina. In vitro, T lymphocytes isolated from oxygen-exposed neonates induced a FasL-mediated apoptosis of hyperoxygenated endothelial cells. Targeting these pathways may prove useful in the treatment of retinal ischemia, a leading cause of vision loss and blindness.

Animals↗
PubMed2003

Optic disc excavation in the atrophic stage of Leber's hereditary optic neuropathy: comparison with normal tension glaucoma.

BACKGROUND: Abnormal optic disc excavations are reportedly seen in patients with Leber's hereditary optic neuropathy (LHON), a mitochondrial dysfunction disease. We examined the disc morphology in the eyes of patients with LHON at the atrophic stage and compared it to that in eyes with normal-tension glaucoma (NTG). METHODS: We studied 15 LHON patients with the 11778 mutation, 15 patients with NTG, and 25 normal subjects. The optic disc morphology was analyzed by Heidelberg retinal tomography (HRT). Ten parameters of the optic disc obtained by HRT were evaluated, including the diagnostic classification of glaucoma. RESULTS: Six of the nine morphological HRT parameters of the LHON patients, the exceptions being disc area, mean cup depth, and maximum cup depth, differed significantly from those of the normals. NTG patients had a significantly greater mean and maximum cup depth than LHON patients. The HRT glaucoma diagnostic software classified 22 (73%) of the 30 optic discs in LHON patients as glaucomatous. CONCLUSION: The optic discs at the atrophic stage of LHON eyes have glaucoma-like morphological changes. However, the cups were significantly deeper in NTG than LHON. The similarity in the optic disc findings in LHON and NTG suggests that alterations in mitochondrial function may be related to optic disc excavations.

Adolescent↗
PubMed2003

Visualization of gaseous monoxide reception by soluble guanylate cyclase in the rat retina.

Immunohistochemistry using novel monoclonal antibodies (mAbs) allowed us to uncover tissue activities of soluble guanylate cyclase (sGC) fine tuned by NO and CO. Upon NO and CO applications in vitro, purified sGC increased the affinity to mAb3221 by 100- and 10-fold, respectively, but not to mAb28131. Immunohistochemistry for gas-generating enzymes revealed that NO occurred in amacrine, bipolar, and Müller's glia cells (MGCs), whereas CO was derived mostly from heme oxygenase (HO)-2 in MGCs. Basal sGC immunoreactivities in vivo to mAb3221 but not to mAb28131 were enhanced by injecting L-arginine and attenuated by blocking NO synthases, suggesting the ability of the former mAb to sense NO. Comparison of mAb-assisted immunohistochemistry suggested that sGC activities were enhanced by zinc protoporphyrin-IX, an HO inhibitor, and repressed completely by blocking NO. However, suggested roles of CO played in situ varied among different retinal layers. In inner plexiform and inner nuclear layers located in the proximity of the cellular NO sources, CO serves as a simple inhibitor of local sGC, while playing roles in housekeeping sGC activation in external limiting membrane standing far from them. These results suggest that CO generated in MGCs is a diffusible gas mediator regulating sGC in both autocrine and paracrine manners.

Animals↗
PubMed2003

Production and activation of matrix metalloproteinase-2 in proliferative diabetic retinopathy.

PURPOSE: To investigate the matrix metalloproteinase (MMP) species and their activation associated with the pathogenesis of proliferative diabetic retinopathy (PDR). METHODS: Sandwich enzyme immunoassays were used to measure concentrations of MMP-1, -2, -3, -7, -8, -9, and -13 in vitreous samples from patients with PDR and nondiabetic vitreoretinal diseases. To evaluate activation ratios of the zymogen of MMP-2 (proMMP-2) and -9 (proMMP-9) in the vitreous samples and fibrovascular tissues, gelatin zymography was performed. Production and tissue localization of MMP-2, membrane type 1-MMP (MT1-MMP), tissue inhibitor of metalloproteinases (TIMP)-2, and MMP-9 in the fibrovascular tissues were examined by immunohistochemistry. mRNA expression of MT1-MMP in the tissues was determined by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Among the seven different MMPs examined in the vitreous samples, only the levels of MMP-2 and -9 were significantly higher in the PDR samples than in the control. However, activation ratios of proMMP-2 (10.6% +/- 11.8%) and proMMP-9 (2.5% +/- 5.1%) in PDR vitreous samples were low and not significantly different from those of the control. In contrast, high activation ratios of proMMP-2 (54.3% +/- 13.6%) and notable activation of proMMP-9 (19.5% +/- 7.8%) were observed in the fibrovascular tissues. Immunohistochemical study demonstrated the localization of MMP-2 and -9 in the endothelial cells and glial cells of the fibrovascular tissues. MMP-2 was colocalized with MT1-MMP and TIMP-2, which are an activator and an activation-enhancing factor, respectively, for proMMP-2. RT-PCR analysis indicated the gene expression of MT1-MMP in the tissues. CONCLUSIONS: These data demonstrate that proMMP-2 is efficiently activated in the fibrovascular tissues of PDR, probably through interaction with MT1-MMP and TIMP-2, and suggest the possibility that the activity of MMP-2 and MT1-MMP is involved in the formation of the fibrovascular tissues.

Adult↗
PubMed2003

Periductal area as the primary site for T-cell activation in lacrimal gland chronic graft-versus-host disease.

PURPOSE: To examine immune processes in the lacrimal gland of patients with chronic graft-versus-host disease (cGVHD) by evaluating the expression of surface molecules associated with T-cell activation. METHODS: Antibodies to CD4, CD8, CD34, CD40, CD54, CD80, CD86, CD154, and HLA-DR were used for immunohistochemical analysis of lacrimal gland biopsy specimens obtained from nine patients with cGVHD and five with Sjögren's syndrome (SS). The regions of interest were further assessed by transmission electron microscopy. RESULTS: CD4(+) and CD8(+) T cells were mainly detected in the periductal areas of the glands of patients with cGVHD, but were distributed throughout the acinar areas in patients with SS. In the periductal areas of patients with cGVHD, a subpopulation of CD4(+) and CD8(+) T cells expressed the activation marker CD154. In addition, CD4(+) and CD8(+) T cells were colocalized with mononuclear infiltrates and stromal fibroblasts expressing the full component of surface molecules necessary for antigen presentation, including HLA-DR, CD54, CD40, CD80, and CD86. Electron microscopy revealed activated fibroblasts that embraced lymphocytes and macrophages with their processes. Also, there were more CD8(+) T cells in the glandular epithelia of patients with cGVHD than in those with SS. Intraepithelial T cells were attached to epithelial cells by several primitive contacts and colocalized with dead cells. CONCLUSIONS: The results strongly suggest that CD4(+) and CD8(+) T cells in the lacrimal glands of patients with cGVHD are primarily activated in the periductal area through antigenic stimulation by potent antigen-presenting cells and stromal fibroblasts, and exert various effector functions, including cytotoxic effects on glandular epithelial cells.

Adult↗
PubMed2003

VEGF164 is proinflammatory in the diabetic retina.

PURPOSE: The objectives of this study were to characterize the differential potency of two major VEGF isoforms, VEGF(120) and VEGF(164), for inducing leukocyte stasis (leukostasis) within the retinal vasculature and blood-retinal barrier (BRB) breakdown and to determine whether endogenous VEGF(164) mediates retinal leukostasis and BRB breakdown in early and established diabetes. METHODS: Retinal leukostasis and BRB breakdown were simultaneously quantified by combining concanavalin A lectin (ConA) perfusion labeling with a fluorophotometric dextran leakage assay. CD45 immunohistochemistry was performed to confirm that ConA-stained cells within the vasculature were leukocytes. Retinal leukostasis and BRB breakdown were compared in nondiabetic rats receiving intravitreous injections of VEGF(120) or VEGF(164). Retinal intercellular adhesion molecule (ICAM)-1 and VEGF protein levels were studied by Western blot and ELISA, respectively. An anti-VEGF(164(165)) aptamer (EYE001) was administered by intravitreous injection to 2-week and 3-month diabetic rats, and the effect on retinal leukostasis and BRB breakdown was quantified. RESULTS: Compared with VEGF(120), VEGF(164) more potently increased retinal ICAM-1 levels (2.2-fold), leukostasis (1.9-fold), and BRB breakdown (2.1-fold, P < 0.01 for all), despite negligible differences in vitreoretinal VEGF levels at the time of evaluation (P > 0.05). Retinal leukostasis and leakage increased with the duration of diabetes (P < 0.01) and correlated closely (P < 0.01, r = 0.889). The isoform-specific blockade of endogenous VEGF(164) with EYE001 resulted in a significant suppression of retinal leukostasis and BRB breakdown in both early (72.4% and 82.6%, respectively) and established (48.5% and 55.0%, respectively) diabetes (P < 0.01). CONCLUSIONS: On an equimolar basis, VEGF(164) is at least twice as potent as VEGF(120) at inducing ICAM-1-mediated retinal leukostasis and BRB breakdown in vivo. The inhibition of diabetic retinal leukostasis and BRB breakdown with EYE001 in early and established diabetes indicates that VEGF(164) is an important isoform in the pathogenesis of early diabetic retinopathy.

Animals↗
PubMed2002

ON-pathway disturbance in two siblings.

PURPOSE: To present two clinical cases diagnosed with predominant cone dystrophy and demonstrating early disturbance in the on-centre bipolar cells (ON-pathway). METHODS: Electrophysiological findings are presented in two siblings with predominant cone dystrophy. The subjects showed no remarkable ophthalmoscopic or fluorescein angiographic retinal changes, but demonstrated progressive visual disturbance during their 20s. RESULTS: The electroretinograms (ERGs) showed reduced dark-adapted responses but the positive component of the photopic ERG was absent. Response to 30 Hz flicker was severely reduced. Electroretinograms elicited by long-duration stimuli showed a loss of the b-wave, and the off-response was slightly reduced. In both patients, multifocal ERGs (m-ERGs) were more reduced within the central 10 degrees, where the ON-pathway is normally a major contributor. CONCLUSION: We conclude that these patients may be affected by an abnormality of the synapses of the cone receptors and that their decrease in vision might, at least initially, be due to selective ON-pathway dysfunction.

Adult↗
PubMed2002

[Two cases of retinal detachment following laser in Situ keratomileusis repaired by scleral buckling surgery].

BACKGROUND: As laser in situ keratomileusis (LASIK) becomes the treatment of choice in the field of refractive surgery, postoperative rhegmatogenous retinal detachment has also begun to occur. However, since it has not been reported yet here in Japan, we report two cases of retinal detachment following LASIK with suggestions based on our experience. CASES: A 34-year-old male(Case 1) and a 26-year-old male(Case 2) suffered from retinal detachment one month and eight months after LASIK, respectively. Contributing retinal breaks were a horseshoe tear in Case 1 and atrophic holes in the lattice degeneration in Case 2. Each patient underwent partial scleral buckling with no intraoperative complication, resulting in successful retinal reattachment. Postoperatively, myopic changes developed and persisted one month in Case 1 and several months in Case 2. CONCLUSIONS: Great attention should be paid to the possibility of postoperative myopia after a repair of retinal detachment following LASIK. Thus, we stress the necessity of close cooperation between LASIK surgeons and vitreoretinal surgeons to settle the matter.

Adult↗
PubMed2002

[The correlation between retinal circulation and function in branch retinal artery occlusion].

PURPOSE: To investigate retinal circulation and function in eyes with branch retinal artery occlusion(BRAO) using a scanning laser Doppler flow-meter (SLDF) and multifocal electroretinogram (mERG). METHODS: In juxtapapillary and paramacular areas close to the occluded artery of the affected eye and the corresponding area of the fellow eye, the mean flow measured by SLDF, indicating microcirculation, and the p-wave amplitude in the response of mERG, indicating retinal function, were determined in three patients with BRAO at the period of reperfusion. The ratios of the affected eye to fellow eye(a/f ratio) were calculated, and the ratios of the mean flow (Fa/f) were compared with those of the p-wave amplitude(Pa/f). RESULTS: In the juxtapapillary area, both Fa/f and Pa/f decreased consistently, but in the paramacular area, Pa/f were lower than Fa/f in all cases. CONCLUSIONS: Functional recovery is likely to be later in the paramacular area than in the juxtapapillary area in the course of recovery of retinal circulation.

Adult↗
PubMedDate not supplied

Multifocal magnetoencephalogram applied to objective visual field analysis.

PURPOSE: To establish an objective visual field analysis by visual evoked magnetic fields. METHODS: Forty-eight focal areas of the visual field were stimulated by the visual evoked response imaging system (VERIS). The multifocal visual evoked magnetic fields (mfVEFs) of 11 healthy subjects were recorded. The output signals were recorded with VERIS, and the second-order kernel was calculated. The equivalent current dipoles (ECDs) were estimated, and the relative positioning of ECDs was determined by a magnetoencephalography (MEG) system. RESULTS: The mfVEFs consisted of either two- or three-peak waves. Large amplitude mfVEFs were elicited when the stimulus was confined to 6 degrees of the central visual field, but a strong response could not always be obtained between 6 degrees and 12 degrees. All ECDs were estimated to originate in the occipital striate cortex. The ECDs for the upper (lower) field stimulations were estimated to be on the lower (upper) cortex, while those for right (left) field stimulations were on the left (right) cortex. CONCLUSIONS: The locations of mfVEF peak ECDs were correlated with the stimulated visual field and generally matched the cruciform model. In combination with the multifocal technique, MEG can be used for objective visual field analysis.

Adult↗
PubMedDate not supplied

Gene analysis and evaluation of the single founder effect in Japanese patients with Oguchi disease.

PURPOSE: To analyze mutations of the arrestin/S-antigen (SAG) gene in nine newly identified Oguchi disease patients, and to examine whether the 926delA (formerly called 1147delA) mutation in the SAG gene is inherited from a single founder. METHODS: DNA samples were assayed for mutations around nucleotide 926 of the SAG gene by direct sequencing, and analyzed for polymorphisms at codon 403 and IVS6-18 of the SAG gene by restriction analysis of polymerase chain reaction products. RESULTS: All nine newly identified patients were homozygous for the 926delA mutation and had the same haplotype at codon 403 and IVS6-18. These findings are identical to those of previous reports of four Japanese Oguchi disease patients. CONCLUSIONS: Mutation 926delA of the SAG gene is the main cause of Oguchi disease in Japanese. This mutation appears to have been inherited from a single founder.

Arrestin↗
PubMedDate not supplied

Retinal blood flow in the macular area before and after scleral buckling procedures for rhegmatogenous retinal detachment without macular involvement.

PURPOSE: To investigate retinal microcirculation changes in patients with rhegmatogenous retinal detachment (RRD). METHODS: The tissue blood flow in the macular area was measured in 28 patients with RRD without macular involvement by scanning laser Doppler flowmetry before and after scleral buckling procedures. The mean blood flow (MBF) was calculated by the automatic full-field analysis program. The MBF ratios of the affected eye to the fellow eye (a/f ratio) in patients were compared with those of the right eye to the left eye (R/L ratio) in the control subjects. RESULTS: The mean preoperative a/f ratio in the patients (0.81 +/- 0.11) was lower than the mean R/L ratio in the control subjects (1.02 +/- 0.11, P < 0.0001) and correlated with the extent of RRD (P < 0.05). The mean a/f ratio tended to decrease 2 weeks after surgery (0.72 +/- 0.09) and recovered to an almost normal level after 1 month (0.96 +/- 0.09). The blood-flow change was not influenced by the type of buckling. CONCLUSIONS: The retinal microcirculation in the macular area was disturbed in RRD patients without macular involvement. It correlated with the extent of the RRD, and subsided 1 month after successful scleral buckling procedures.

Adolescent↗