Biomedical subjects

Makoto Tamai

Publications and source records attributed to Makoto Tamai.

At least 19 recordsLinked to original sources

PubMed2006

Polymorphisms in Complement Factor H and Hemicentin-1 genes in a Japanese population with dry-type age-related macular degeneration.

PURPOSE: To determine whether polymorphisms in the Complement Factor H (CFH) gene and the Hemicentin-1 gene at the ARMD1 locus are associated with dry age-related macular degeneration (AMD) in Japanese patients. DESIGN: Clinically relevant laboratory investigation. METHODS: Eighty unrelated Japanese patients with dry AMD and 196 Japanese control patients were studied. Two exons of the CFH gene and four exons of the Hemicentin-1 gene were amplified by polymerase chain reaction and sequenced directly. RESULTS: For the CFH gene, the frequency of the previously reported Tyr402His variant was not significantly higher in the AMD group than in the control group (P = .31). In the Hemicentin-1 gene, three sequence alterations (Asp5088Val, IVS99-13C/T, and His5245Gln) were detected, and the originally reported Gln5346Arg was not detected. CONCLUSION: The CFH gene and Hemicentin-1 genes do not appear to be involved in a statistically significant fraction of dry AMD cases in the Japanese population.

Aged↗

PubMed2006

Screening of the MERTK gene for mutations in Japanese patients with autosomal recessive retinitis pigmentosa.

PURPOSE: To determine whether mutations in the MERTK gene are present in Japanese patients with autosomal recessive retinitis pigmentosa (arRP). METHODS: The coding sequence of all 19 exons and the adjacent flanking intron sequences of the MERTK gene were directly sequenced in 96 unrelated Japanese patients with arRP. RESULTS: Seventeen sequence variants were found; six missense changes, three isocoding changes, and eight intron changes were also observed. One arRP patient had a novel homozygous Leu12Pro missense mutation in the MERTK gene. CONCLUSIONS: Mutations in the MERTK gene are relatively rare in Japanese patients with arRP.

Asian People↗

PubMed2006

Neuroprotective effect of latanoprost on rat retinal ganglion cells.

BACKGROUND: To investigate the neuroprotective effect of intravitreal administration of latanoprost on retinal ganglion cell (RGC) damage induced by N-methyl-D-aspartic acid (NMDA) or optic nerve axotomy. METHODS: Using Sprague-Dawley rats, retinal ganglion cell damage was induced by either intravitreal administration of NMDA or optic nerve axotomy. Latanoprost at doses of 0.03, 0.3, 3, 30 and 300 pmol was administered intravitreally before NMDA injection or optic nerve axotomy. Retinal damage was evaluated by counting the number of surviving RGCs retrogradely labeled with fluorogold under the microscope. RESULTS: Seven days after the NMDA injury, the number of surviving RGCs was significantly increased at doses of more than 30 pmol atanoprost (846+/-178 cells/mm(2 ) P=0.0166) compared with vehicle control (556+/-122 cells/mm(2)). Ten days after the optic nerve axotomy, the number of surviving RGC was significantly increased even at a dose of 0.3 pmol (815+/-239 cells/mm(2), P=0.0359) compared with control (462+/-75 cells/mm(2)). CONCLUSIONS: Intravitreal administration of latanoprost has a neuroprotective effect on rat RGC damage induced by either NMDA or optic nerve axotomy, while its pharmacological features are different.

Animals↗

PubMed2006

Hypothermia of 8 degrees C protects cultured retinal pigment epithelial cells and retinal ganglion cells against trypan blue toxicity.

PURPOSE: To determine whether hypothermia of 8 degrees C can protect cultured human retinal pigment epithelial (ARPE-19) cells and rat retinal ganglion cells (RGC-5) against trypan blue (TB) toxicity. DESIGN: Laboratory investigation. METHODS: ARPE-19 cells and RGC-5 were exposed to balanced salt solution as controls, and 0.05% and 0.5% TB at 37 degrees C, and at 8 degrees C for one minute. The percentage of surviving cells was determined by the resazurin test. RESULTS: TB induced a statistically significant decrease in the percentage of ARPE-19 cells surviving at 0.5% TB at 37 degrees C (P < .01). Conversely, TB induced a statistically significant decrease in the percentage of RGC-5 surviving at all conditions except for 0.05% TB at 8 degrees C (0.05% 37 degrees C; P < .05, 0.5% 37 degrees C and 8 degrees C; P < .01). CONCLUSIONS: These results indicate that reducing the temperature to 8 degrees C has a protective effect against the TB toxicity for ARPE-19 cells and RGC-5 in culture.

Animals↗

PubMed2006

Anatomic study of arborization patterns of the ulnar artery in Guyon's canal.

PURPOSE: To show variations in arborization patterns of the ulnar artery in Guyon's canal and to investigate the relationship between the hypothenar muscles and the ulnar artery. METHODS: Thirty-five embalmed cadaveric hands were dissected and the existence and course of the superficial and deep palmar branches of the ulnar artery and the site of feeding branches to the hypothenar muscles were recorded. The anatomic relationship between the ulnar artery and the hypothenar muscle variations also was investigated. RESULTS: Four arborization patterns were identified. In type 1UA (n = 17 hands), an artery accompanying the deep branch of the ulnar nerve (AADBUN) formed a deep palmar arch (DPA). In type 2UA (n = 11 hands) the AADBUN continued to the feeding artery of the abductor digiti minimi and the distal deep palmar branch of the ulnar artery (DDPBUA) branched off distally. This arterial structure formed a DPA. In type 3UA (n = 6 hands) both the AADBUN and DDPBUA formed DPAs. In type 4UA(n = 1 hand), the AADBUN continued to the feeding artery of the abductor digiti minimi with no DDPBUA and therefore no DPA. A dorsal perforating artery of the ulnar artery also was found in 4 hands. This branch came from the AADBUN at the level of the distal edge of the pisiform and merged with the dorsal carpal arterial arch. We also investigated the relationship between the structural pattern of the hiatus for the deep branch of the ulnar nerve and ulnar artery variation but found no association. The most common pattern observed was a type 1 hiatus with a type 1UA arborization pattern. CONCLUSIONS: Our study confirmed considerable variations in the arborization pattern of the ulnar artery in Guyon's canal. To avoid injury to the arterial branches during surgery in this region care must be taken with respect to variations of the ulnar artery in Guyon's canal.

Cadaver↗

PubMed2006

Abnormal migration and distribution of neural crest cells in Pax6 heterozygous mutant eye, a model for human eye diseases.

PAX6/Pax6 gene encodes a transcription factor that is crucially required for eye development. Pax6 heterozygous mutant mouse (Pax6(Sey/+)) shows various ocular defects, especially in the anterior segment. It has been well known that the induction of the lens and development of the cornea and retina are dependent on PAX6/Pax6 in a cell-autonomous fashion, although the influence of PAX6/Pax6 on the other tissues derived from the ocular mesenchyme is largely unknown. Using transgenic mouse lines in which neural crest cells are genetically marked by LacZ or EGFP, we revealed the extensive contribution of neural crest derived cells (NCDCs) to the ocular tissues. Furthermore, various eye defects in Pax6(Sey/+) mouse were accompanied by abnormal distribution of NCDCs from early developmental stages to the adult. In Pax6(Sey/+) mouse mice, neural crest cells abnormally migrated into the developing eye in a cell nonautonomous manner at early embryonic stages. These results indicate that normal distribution and integration of NCDCs in ocular tissues depend on a proper dosage of Pax6, and that Pax6(Sey/+) eye anomalies are caused by cell autonomous and nonautonomous defects due to Pax6 haploinsufficiency.

Animals↗

PubMed2006

Hypothermia protects cultured human retinal pigment epithelial cells against trypan blue toxicity.

PURPOSE: To determine whether trypan blue (TB) is toxic to cultured human retinal pigment epithelial (ARPE-19) cells, and whether hypothermia can protect ARPE-19 cells against TB toxicity. METHODS: ARPE-19 cells were cultured and exposed to balanced salt solution as a control, while other cells were exposed to 0.05, 0.2, and 0.5% TB dye at 37 and 4 degrees C for 5 and 30 min. The percentage of ARPE-19 cells that survived was determined by resazurin 1 day after the exposure. RESULTS: A statistically significant decrease in the percentage of ARPE-19 cells surviving was found after exposure to 0.2 and 0.5% TB at any temperature or for any exposure duration (p < 0.01). The percentage of RPE cells surviving at 0.05% was not significantly different from that of controls except for a 30-min exposure at 37 degrees C. The percentage of cells surviving at 4 degrees C for a 5-min exposure to 0.5% TB and a 30-min exposure to 0.2 and 0.5% was significantly higher than that at 37 degrees C under each condition (p < 0.01 for all). CONCLUSIONS: These results indicate that TB is toxic to human RPE cells, and the toxicity is dose- and exposure duration-dependent. Exposing the cells at 4 degrees C had a protective effect against higher concentrations or longer exposure durations of TB compared to exposure at 37 degrees C.

Cell Count↗

PubMed2006

Evaluation of indocyanine green toxicity to rat retinas.

PURPOSE: To investigate the toxicity of indocyanine green (ICG) on retinal cells using cultured retinal pigment epithelium (RPE) cells and the effects of intravitreous injection of ICG into rat eyes. METHODS: Cultured RPE cells were exposed to various concentrations of ICG for 2 min, a viability assay was performed 1 day after exposure. For an in vivo study, 5 microl of ICG (5 or 25 mg/ml) were injected into the vitreous cavity of rat eyes, which were examined 1, 3 and 7 days after the injection by histological and glutamine synthetase (GS) immunohistological evaluation. RESULTS: Viabilities of RPE cells were decreased dependent on the ICG dose. In the histological evaluation, we observed differences of effects of ICG between the central retinal area and the peripheral area. ICG injection caused degeneration of all retinal layers in the central retinal area. GS immunoreactivities decreased by ICG injection, which corresponded to an area of severe destruction. CONCLUSION: A high concentration of ICG may cause toxic effects on retinal cells. Mueller cell dysfunction may play some role in the retinal toxicity caused by ICG.

Animals↗

PubMed2006

Recombinant AAV-transduced iris pigment epithelial cell transplantation may transfer vector to native RPE but suppress systemic dissemination.

PURPOSE: To determine whether adenoassociated virus (AAV) vectors transduced into iris pigment epithelial (IPE) cells and transplanted into the subretinal space of rats will transfer the AAV genome to the host cells and whether the vectors are disseminated systemically. METHODS: Recombinant (r)AAV was transduced into rat IPE cells and transplanted into the subretinal space of rats. For the control, rAAVs alone were injected subretinally. The transplanted IPE cells were detected by LacZ staining. Immunohistochemistry, electron microscopy, electroretinography, and fluorescein-dextran angiography were performed. DNA was extracted from various organs and blood and examined for the AAV genome by polymerase chain reaction. RESULTS: No toxicity from rAAV transduction was observed in vitro. LacZ was expressed in the transplanted cells 1 and 2 weeks after transplantation. At 4 and 12 weeks, fewer transplanted cells were detected than at 1 week, and LacZ expression was occasionally detected at the level of host retinal pigment epithelial (RPE) cells. Expression was also detected in ciliary body epithelial cells. The electroretinograms and fluorescein-dextran angiography were only mildly altered. Significantly lower levels of AAV genome were detected in the organs and blood of rats receiving rAAV-IPE cell transplants than with direct intravenous injection of AAV vectors. CONCLUSIONS: AAV-mediated LacZ was expressed in the transplanted cells after subretinal transplantation, and the transplanted IPE cells may transfer the rAAV to host tissues, such as RPE cells, long after the transplantation. This method of gene delivery did not lead to systemic dissemination of the vectors.

Animals↗

PubMed2006

Visual function with acupuncture tested by visual evoked potential.

Visual evoked potential (VEP) testing is used frequently and is an important ophthalmologic physiological test to examine visual functions objectively. The VEP is a complicated waveform consisting of negative waveform named N75 and N135, and positive waveform named P100. Delayed P100 latency and greatly attenuated amplitude on VEP are known characteristics for diagnosing optic nerve disease. Acupuncture has been used to treat wide clinical symptoms with minimal side effects. The confirmation of the efficacy of acupuncture generally relies on subjective symptoms. There is not much scientific evidence supporting the acupuncture treatments for eye diseases up to today. However, the VEP test can evaluate objectively and numerically the efficacy of the treatment by the acupuncture. We analyzed 19 healthy subjects (38 eyes). The P100 latencies in the group of less than 101.7 msec (total average) before acupuncture stimulations were not different than those after treatment (98.2 +/- 3.0 msec, 98.2 +/- 4.0 msec, respectively, p = 0.88, n = 17), but the latencies in those subjects with longer or equal to 101.7 msec were statistically different after acupuncture (104.6 +/- 2.8 msec, 101.9 +/- 3.7 msec, respectively, p = 0.006, n = 21). These results show that the acupuncture stimulation contributes to the P100 latencies of pattern reversal (PR)-VEP to some subjects who have delayed latencies, and this electrophysiological method is a valuable technique in monitoring the effectiveness of acupuncture therapy in the improvements of visual functions. The purpose of this study is to evaluate the physiological effects by acupuncture stimulations using PR-VEP in normal subjects.

Acupuncture Therapy↗

PubMed2005

N-Methyl-D-Aspartic acid suppresses Akt activity through protein phosphatase in retinal ganglion cells.

PURPOSE: To investigate the relationship between Akt activity and retinal ganglion cell (RGC) death induced by N-Methyl-D-Aspartic acid (NMDA) in the rat retina. METHODS: Two microlitres of 1, 10, 50, 100, or 200 mM NMDA, or vehicle was injected into the vitreous cavity of Sprague-Dawley (SD) rats (n=125). Retinal damage was estimated by counting ganglion cells labeled with fluorochrome and retinal apoptosis was detected by TUNEL. Akt activity was determined by immunohistochemical analysis with a specific antibody to the activated (phosphorylated) form of Akt. To investigate the mechanism of dephosphorylation of Akt, Okadaic acid, a potent protein phosphatase inhibitor, was injected 1 h before NMDA injury and accessed the number of phosphorylated Akt positive cells 1 h after NMDA injection. To stimulate Akt activity in the retina, brain derived neurotrophic factor (BDNF) was injected into the vitreous 15 min before NMDA injection. RESULTS: Immunohistochemical analysis revealed a reduction in phosphorylated Akt in RGCs and amacrine cells one hour after NMDA injury. The RGCs and amacrine cells showed TUNEL positivity at 6 h and a decrease in cell number at 7 days after NMDA injury. No other cells in the retina stained positive with phosphorylated Akt antibody and TUNEL. Okadaic acid prevented the dephosphorylation of Akt by NMDA. The exogenous administration of BDNF prevented the dephosphorylation of Akt in N-Shc/ShcC-positive RGCs and significantly suppressed the NMDA-induced RGC death. CONCLUSIONS: These observations suggest that Akt is one of the key signaling proteins in RGC death induced by NMDA, and that the presence of N-Shc/ShcC enhances BDNF-mediated neuroprotection via phosphorylated Akt. The regulation of phosphorylated Akt by growth factors and protein phosphatase activity may play an important role in cell fate following NMDA injury. Thus, an increase in phosphorylated Akt may have potential therapeutic implications in the treatment of glutamate-related disease.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Selective upregulation of RB3/stathmin4 by ciliary neurotrophic factor following optic nerve axotomy.

In this study, we examined the cellular responses of stathmin-related proteins in the rat retina following optic nerve (ON) axotomy. To examine the distribution of stathmin-related gene products, we performed semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization (ISH) and immunohistochemical analyses. Retrograde labeling using a fluorescein tracer, fluorogold (FG), was used for the identification of retinal ganglion cells (RGCs). RT-PCR and ISH analyses indicated that the expression of RB3 was specifically increased in the ganglion cell layer (GCL) comparing to other members of stathmin-related gene family examined 3 days following the ON axotomy. When brain-derived neurotrophic factor was administrated intravitreously, the induction of RB3 mRNA sustained up to 7 days after axotomy, although the peak induction level was unchanged. In contrast, ciliary neurotrophic factor (CNTF) administration increased the peak level of RB3 mRNA induction significantly at 3 days after axotomy. Immunohistochemistry in combination with the retrograde labeling of axotomized cells by FG revealed that RB3 was increased following axotomy in FG-labeled RGCs. These data suggest that RB3 is the unique response protein in the stathmin-related proteins following ON axotomy and the induced RB3 may play a critical role in the CNTF-induced response on the axotomized RGCs, e.g. axonal regeneration and/or neuroprotection.

Animals↗

PubMed2005

Cilioretinal artery occlusions following embolization of an artery to an intracranial meningioma.

PURPOSE: To report a case in which a prophylactic embolization of a feeder artery to an intarcranial meningioma led to an occlusion of a cilioretinal artery. DESIGN: A case report. METHODS: A 48-year-old man with an intracranial meningioma presented with ocular pain and visual loss in his right eye following embolization of a feeder artery to the meningioma with polyvinyl alcohol. RESULTS: Ophthalmoscopy 1 month later showed a cilioretinal artery occlusion which was confirmed by fluorescein angiography. His visual acuity was 0.01 in the right eye. The patient was not treated for his ocular symptoms, and his visual acuity 9 month postoperatively improved slightly to 0.1. CONCLUSIONS: Our case demonstrated that an occlusion of a retinal artery can be a complication of preoperative embolization of an artery to an intracranial tumor and can lead to severe visual loss.

Arterial Occlusive Diseases↗

PubMed2005

Retinal G-substrate, potential downstream component of NO/cGMP/PKG pathway, is located in subtype of retinal ganglion cells and amacrine cells with protein phosphatases.

The aim of this study was to determine the distribution and function of G-substrate, a specific substrate of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-cGMP-dependent protein kinase (PKG) signaling pathway, in normal rat retina and in G-substrate knockout mice. The retinas of adult wild-type rats and mice and G-substrate knockout mice were studied immunohistologically to characterize the upstream and downstream components of the NO-cGMP-PKG pathway. Immunoblot analysis showed that the molecular weight of retinal G-substrate was similar to that of cerebellar G-substrate. In adult rats and mice, retinal G-substrate was located in a subpopulation of amacrine cells and in C38-positive retinal ganglion cells (RGCs) but not in alpha RGCs. In addition, retinal G-substrate was co-expressed with other upstream and downstream signaling components of the NO-cGMP-PKG-G-substrate-phosphatase pathway in the adult retina. Electroretinographic (ERG) analysis demonstrated that there was no significant difference between the ERGs of wild-type and G-substrate knockout mice. These results suggest that retinal G-substrate plays a role as a downstream component of the NO-cGMP-PKG pathway. The co-localization of retinal G-substrate with protein Ser/Thr phosphatases suggests that it acts as an endogenous protein phosphatase inhibitor as in the cerebellum.

Amacrine Cells↗

PubMed2005

Screening for mutations in CYP4V2 gene in Japanese patients with Bietti's crystalline corneoretinal dystrophy.

PURPOSE: To describe the clinical and genetic characteristics of six Japanese families with Bietti's crystalline corneoretinal dystrophy (BCD). DESIGN: Case reports and results of DNA analysis. METHODS: Mutation screening was performed on six unrelated patients with BCD by direct sequencing. The clinical features were characterized by the visual acuity, slit-lamp biomicroscopy, electroretinography, fluorescein angiography, and kinetic visual field testing. RESULTS: An identical IVS6 to 8delTCATACAGGTCATCGCG/insGC mutation in the CYP4V2 gene was identified in five of the patients with BCD; the sixth patient had a novel Trp340X mutation in the CYP4V2 gene. Three patients showed crystalline-like deposits at the limbus by specular microscopy. Ophthalmic findings of all patients had a rapid progression after age 50 years. CONCLUSIONS: Our findings suggest that the IVS6 to 8delTCATACAGGTCATCGCG/insGC mutation is a common mutation in Japanese patients with BCD. Although phenotypic variability was found, the natural course was almost the same in all of our patients.

Adult↗

PubMed2005

Screening for mutations in the IMPDH1 gene in Japanese patients with autosomal dominant retinitis pigmentosa.

PURPOSE: To determine the presence and frequency of mutations in the IMPDH1 gene in Japanese patients with autosomal dominant retinitis pigmentosa (ADRP), and to characterize the clinical characteristics of patients with the Lys238Arg mutation in the IMPDH1 gene. DESIGN: Case reports and results of DNA analysis. METHODS: All 14 coding exons of the IMPDH1 gene were directly sequenced in 96 unrelated patients with ADRP. The clinical features were determined by visual acuity, slit-lamp biomicroscopy, and kinetic visual field tests. RESULTS: Two novel mutations, a Leu227Pro and Lys238Arg, in the IMPDH1 gene were identified in two unrelated families with ADRP. The clinical features associated with the Lys238Arg mutation were an early-onset and severe retinal degeneration. CONCLUSIONS: The most commonly reported Asp226Asn mutation was not found in the Japanese population, instead two novel mutations were found. These findings suggest that mutations of the IMPDH1 gene cause ADRP in the Japanese population.

Adult↗

PubMed2005

Visual dysfunction after panretinal photocoagulation in patients with severe diabetic retinopathy and good vision.

PURPOSE: To compare macular thickness and best-corrected visual acuity (BcVA) before and after panretinal photocoagulation (PRP) in patients with severe diabetic retinopathy and good visual acuity (VA) to identify factors that predict post-operative visual function. DESIGN: Prospective, non-comparative, interventional case series. METHODS: Sixty-four consecutive patients with severe non-proliferative diabetic retinopathy or with non-high-risk proliferative diabetic retinopathy whose VA was 20/20 or better before PRP were studied. Sixty-four eyes of 64 patients underwent scatter PRP in four sessions every other week. Macular thickness was measured by optical coherence tomography (OCT), and VA was measured before and periodically after PRP. RESULTS: During the 24-week observation period, patients were classified into three groups according to changes in VA during the post-operative period. In group A, VA was maintained at pre-operative levels in 54 (84%) eyes during the 24 weeks after PRP. In group B, VA initially decreased in three eyes but subsequently recovered to baseline during the observation period; in group C, VA did not recover during follow-up in seven eyes. There was no significant difference in pre-operative foveal thicknesses among the three groups, but parafoveal thickness was <260 mum in group A, ranged from 270 to 280 mum in group B, and was >300 mum in group C. CONCLUSION: For eyes with severe diabetic retinopathy and good VA, PRP did not affect post-operative VA in more than 80% of patients. Patients whose pre-operative parafoveal thickness was >300 mum had a worse visual prognosis.

Adult↗

PubMed2005

Mutations in the pre-mRNA splicing gene, PRPF31, in Japanese families with autosomal dominant retinitis pigmentosa.

PURPOSE: To describe the clinical and genetic characteristics of three Japanese families with autosomal dominant retinitis pigmentosa (ADRP) associated with mutations in the PRPF31 gene. DESIGN: Case reports and results of DNA analysis. METHODS: Mutational screening of the PRPF31 gene was performed on 96 unrelated patients with ADRP by direct sequencing. The clinical features were characterized by complete ophthalmologic examinations. RESULTS: Three mutations in the PRPF31 gene, designated as 1142delG, 1155-1159delGGACG/insAGGGATT, and IVS6 to 3 to -45del, were identified in three unrelated Japanese families with ADRP. The 1142delG and 1155-1159delGGACG/insAGGGATT mutations are novel. The phenotype of affected family members was typical of retinitis pigmentosa (RP). Additionally, we identified asymptomatic obligate carriers. CONCLUSIONS: The 1142delG and 1155-1159delGGACG/insAGGGATT mutations in the PRPF31 gene cause RP. The prevalence of mutations in the PRPF31 gene in Japanese patients with ADRP is approximately 3%. However, it is important to note that there are asymptomatic obligate carriers.

Aged↗