Biomedical subjects

Kazuhide Kawase

Publications and source records attributed to Kazuhide Kawase.

7 recordsLinked to original sources

PubMed2006

Ethnic variation in AMD-associated complement factor H polymorphism p.Tyr402His.

Age-related macular degeneration (AMD) is the most common cause of irreversible visual loss in the developed world. Previous studies have demonstrated that the c.1204T>C, p.Tyr402His allelic variant in the complement factor H (CFH) gene is associated with an approximately three-fold increased risk for AMD in Caucasians of predominantly European descent. Both the prevalence as well as the phenotypic spectrum of AMD varies widely among persons of different ethnicities. We hypothesized that populations with a lower prevalence of AMD might also have a lower prevalence of the CFH risk allele. In this study we sought to determine the frequency of this sequence variant in control populations of Caucasians, African Americans, Hispanics, Somalis, and Japanese. Normal control populations were assembled for each ethnic group: Caucasian (n=148), Somali (n=128), African American (n=75), Hispanic (n=81), and Japanese (n=82). Individuals were genotyped using a restriction digest assay and the frequency of the C allele at nucleotide position 1204 of the CFH gene was determined. A bioinformatic approach was used to identify SNPs in linkage disequilibrium with rs1061170 (c.1204T>C, p.Tyr402His) from the human haplotype map project database (HapMap) in order to validate the findings. We found widely discordant frequencies of the risk allele between some of the different ethnic groups: Japanese 0.07+/-0.02, Hispanics 0.17+/-0.03, African-Americans 0.35+/-0.04, Caucasians 0.34+/-0.03, and Somalis 0.34+/-0.03. Allele frequencies generated by analysis of the HapMap database were consistent with these findings. This study suggests that there are other yet unidentified genetic factors important in the pathogenesis of AMD that may mitigate the effects of c.1204T>C, p.Tyr402His variant.

Aged↗

PubMed2006

Metallothionein, an endogenous antioxidant, protects against retinal neuron damage in mice.

PURPOSE: To clarify the functional role of metallothionein (MT) in retinal damage in mice deficient in both MT-I and -II (MT-I/-II-deficient mice [C57BL/6J background]) and wild-type (C57BL/6J) mice and MT induction (zinc sulfate [ZnSO4] and 1alpha, 25-dihydroxyvitamin D3 [Vit. D3]). METHODS: Retinal, cell damage was induced by intravitreous injection of N-methyl-D-aspartate (NMDA; 40 nmol/eye). Retinal MT-I, -II, and -III mRNA expression was monitored by real-time reverse-transcription-PCR of total retinal RNA from eyes injected or not injected with NMDA. In wild-type mice, MT-I and -II immunohistochemistry was performed (with antibody that recognizes both proteins) 12 and 24 hours after intravitreous NMDA injection. To examine the involvement of induced retinal MT, ZnSO4 (10 nmol/eye) or Vit. D3 (0.2 or 2 ng/eye) was intravitreously injected 24 hours before NMDA injection in wild-type or MT-I/-II-deficient mice, and ganglion cell layer (GCL) cell loss and inner plexiform layer (IPL) thinning were evaluated 7 days after the NMDA injection. The protective effect of Vit. D3 was assessed against the RGC-5 cell death induced by oxidative stress (using buthionine sulfoximine [BSO] to deplete glutathione in combination with glutamate to inhibit cystine uptake). RESULTS: In wild-type mice, MT-II mRNA expression was time-dependently elevated by NMDA (5.9 and 7.4 times versus the nontreated control at 4 and 12 hours, respectively, after injection), with the normal level being regained within 24 hours. In contrast, MT-I and -III showed persistent decreases (to <50% control) from 4 to 24 hours. In wild-type mice, MT-like immunoreactivity was increased in the inner retina (GCL and IPL) 12 and 24 hours after NMDA injection. At 7 days after NMDA injection in MT-I/-II-deficient mice (versus wild-type mice), GCL cell loss was increased, but IPL thickness was not different. Pretreatment with ZnSO4 or Vit. D3 increased inner retinal MT-like immunoreactivity 24 hours after NMDA injection and significantly attenuated NMDA-induced GCL cell loss in wild-type mice, but ZnSO4 pretreatment did not protect against such cell loss in MT-I/-II-deficient mice. In vitro, Vit. D3 pretreatment (100 nM) reduced BSO+glutamate-induced RGC-5 cell death. CONCLUSIONS: These findings suggest that MT, especially MT-II, protects against retinal neuron damage, by acting as an endogenous antioxidant.

Animals↗

PubMed2004

Optic disc hemorrhages detected in a large-scale eye disease screening project.

PURPOSE: To investigate the prevalence and characteristics of optic disc hemorrhages. MATERIALS AND METHODS: We took IMAGEnet fundus photographs of 14,779 participants, aged 40 years or older in a large-scale eye disease screening project conducted in Tajimi, Japan. A single researcher reviewed all of the photographs for the presence of ocular abnormality in the optic nerve head and retina, paying special attention to the presence or absence of optic disc hemorrhages. Glaucomatous optic neuropathy was diagnosed based on the presence of nerve fiber layer defects and/or the appearance of the optic disc. RESULTS: Fundus photographs of 13,965 cases (27,930 eyes) were successfully reviewed bilaterally. We found disc hemorrhages at 92 locations of 92 (0.3%) eyes of 88 (0.6%) cases. Twenty-four hemorrhages of 23 (26%) cases were found in bilateral non-glaucoma cases and the remaining 68 hemorrhages of 65 (74%) cases were found in glaucoma cases. The prevalence of disc hemorrhages was 8.2% in 793 glaucoma cases and 0.2% in non-glaucoma cases. Hemorrhages developed significantly more frequently in females and in the elderly. The hemorrhages were predominantly found in the inferotemporal and superotemporal regions. The intraocular pressure was less than 20 mm Hg in all cases. The mean intraocular pressure was 15.0 mm Hg for glaucoma cases with hemorrhages and 13.9 mm Hg for non-glaucoma cases with hemorrhages. CONCLUSION: Disc hemorrhages occur more frequently in females, in elderly persons, and in glaucoma cases in Japanese aged 40 or older. The intraocular pressure of the eyes with disc hemorrhages is close to that of the normal population.

Adult↗

PubMed2003

Evaluation of optineurin sequence variations in 1,048 patients with open-angle glaucoma.

PURPOSE: To investigate the association of sequence variations in the optineurin (OPTN) gene in patients with open-angle glaucoma. DESIGN: Prospective case control study. METHODS: The OPTN gene was screened for sequence variations using a combination of single-strand conformational polymorphism analysis and automated DNA sequencing. A total of 1,299 subjects (1048 glaucoma patients and 251 controls) were screened for variations in the four portions of the gene that had been previously associated with glaucoma. A subset of these subjects (376 patients and 176 controls) was screened for variations in the entire coding sequence. Twenty-four percent of the patients and 35% of the controls were Japanese, whereas the remainder were predominantly Caucasian. Allele frequencies were compared with the Fisher exact test. RESULTS: The OPTN sequence variations were not significantly associated with any form of high-tension open-angle glaucoma. One proband with familial normal-tension glaucoma was found to harbor the previously reported Glu50Lys variation. Another previously reported change, Met98Lys, was associated with normal-tension glaucoma in Japanese but not in Caucasian patients. CONCLUSIONS: This study provides some additional evidence for the association of the Glu50Lys OPTN sequence variation with familial normal tension glaucoma. However, because familial normal-tension glaucoma is so rare, this change seems to be responsible for less than 0.1% of all open-angle glaucoma. The Arg545Gln variation is likely to be a nondisease-causing polymorphism. The Met98Lys change may be associated with a fraction of normal-tension glaucoma in patients of Japanese ethnicity.

Base Sequence↗

PubMed2002

Neuronal degradation in mouse retina after a transient ischemia and protective effect of hypothermia.

Temporal profile of neuronal deaths in the mouse retina evoked by a transient retinal ischemia and the protective effect of hypothermia on such deaths were evaluated. A transient ischemic insult was induced in the mouse retina by elevating the intra-ocular pressure. The retina tissue responses after reperfusion were histopathologically detected by monitoring the retinal cell death in the ganglion cell layer and inner nuclear layer, using a sequential TUNEL-staining technique, and by measuring the inner retinal thickness. Elevation of intra-ocular pressure induced a time-related appearance of TUNEL-positive cells in the mouse inner retinas. Peak TUNEL staining occurred 12 h after reperfusion. Lowering mice body temperature to 35 degrees C, 33 degrees C and 29 degrees C during the ischemia period significantly inhibited DNA fragmentation of retinal neurons in a lowering temperature dependent manner. In this experiment, the inner retinal thickness was preserved in 29 degrees C group compared with that in 37 degrees C group. From these results, the 45-min transient ischemia and histopathological examination 12 h later provided a reproducible number of retinal neuronal deaths. Furthermore, hypothermic intervention showed a protective effect to salvage retinal neuronal cells from a transient ischemic insult.

Animals↗

PubMedDate not supplied

Diurnal variation of intraocular pressure in suspected normal-tension glaucoma.

PURPOSE: To assess diurnal variations of intraocular pressure (IOP) in suspected normal-tension glaucoma (NTG) patients with subsequent long-term observation to detect changes that may lead to a new diagnosis. METHODS: Diurnal variation of IOP was measured in a sitting position at 2-h intervals for 24 h in a total of 569 subjects with suspected NTG. RESULTS: Thirty of the 569 subjects (5.3%) showed IOP values exceeding 20 mmHg during the 24-h monitoring and were diagnosed as having primary open-angle glaucoma (POAG). In subjects in whom NTG was definitely diagnosed based on the results of the 24-h monitoring, the average maximum, minimum, and mean IOP was 16.1, 11.7, and 13.9 mmHg, respectively, and the mean diurnal variation in IOP was 4.4 mmHg. The peak time was observed outside clinic hours (1800-0800) in 41.4% of patients, and the trough time was observed during clinic hours (1000-1600) in 15.9%. In 2.9% of NTG subjects, the diagnosis was eventually changed to POAG during follow-up. CONCLUSION: Assessment of diurnal variations of IOP in suspected NTG patients is useful for the differential diagnosis of POAG from NTG and for establishment of a baseline, which may affect the management plan.

Adolescent↗

PubMedDate not supplied

Neuroprotective effects of R(-)-1-(benzo[b]thiophen-5-yl)-2- [2-(N,N-diethylamino)ethoxy]ethanol hydrochloride (T-588) against retinal ganglion cell death induced by elevated intraocular pressure in rat.

PURPOSE: We investigated whether T-588 can attenuate retinal ganglion cell (RGC) death induced by elevated intraocular pressure (IOP). METHODS: IOP elevation was induced unilaterally by argon laser irradiation of the rat trabecular meshwork 4 days after an intracameral injection of India ink. We orally administered either the vehicle, or 10, 30, or 100 mg/kg body weight (BW) of T-588 24 hours before the laser application. Five days after the laser application, 1.5 microL of 3% Fast Blue was injected into the superior colliculi bilaterally. Three days after the Fast Blue injection, the eye was enucleated and the retinal whole flatmount was prepared. Labeled ganglion cells were counted by fluorescence microscope with an ultraviolet filter. RESULTS: Laser treatment significantly increased the IOP. The percentages of labeled RGCs in the lasered eyes as compared with the nonlasered contralateral eyes were 78.0 +/- 11.6% in the control group, 78.7 +/- 12.9% in the 10 mg/kg BW group, 79.1 +/- 13.0% in the 30 mg/kg BW group, and 91.0 +/- 9.0% in the 100 mg/kg BW T-588-treated group. The survival rate of RGCs was significantly higher in the 100 mg/kg BW T-588-treated group than in the control group. CONCLUSION: T-588 appears to have a neuroprotective effect on retinal ganglion cells in this ocular hypertensive model.

Administration, Oral↗