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Biomedical subjects

Takaaki Hayashi

Publications and source records attributed to Takaaki Hayashi.

At least 19 recordsLinked to original sources
PubMed2006

A novel homozygous GRK1 mutation (P391H) in 2 siblings with Oguchi disease with markedly reduced cone responses.

PURPOSE: The only mutations reported to date in Japanese patients with Oguchi disease, a rare form of stationary night blindness with autosomal recessive transmission, have been in the SAG (arrestin) gene. The objective of this study was to describe the ophthalmic features and a novel mutation in the GRK1 (rhodopsin kinase) gene in 2 Japanese patients with Oguchi disease. DESIGN: Molecular genetic and observational case study. PARTICIPANTS: A consanguineous family including 2 siblings with Oguchi disease (a 35-year-old man and a 31-year-old woman). METHODS: Best-corrected visual acuity (BCVA), fundus examinations, Goldmann perimetry, color vision tests, and full-field electroretinograms (ERGs) were evaluated. Mutation screening of the SAG and GRK1 genes was performed with polymerase chain reaction amplification and direct sequencing. MAIN OUTCOME MEASURES: Mutations in the GRK1 gene, BCVA, color vision, fundus photographs, visual fields, and ERG findings. RESULTS: Molecular analysis revealed a novel homozygous missense mutation (p.P391H) in the GRK1 gene in both patients. Proline 391 is not only within the functionally important catalytic domain, but is also a phylogenetically conserved amino acid residue among GRK1 orthologs and homologs. No mutation was found in the SAG gene. The unaffected parents were heterozygous carriers of the mutation. Both patients had night blindness, 1.5 BCVA for each eye, normal color vision, and typical fundus appearance with golden-yellow discoloration. The visual fields were normal in the male sibling. The ERGs showed no rod B waves, reduced standard combined responses, and markedly reduced single-flash cone and 30-Hz flicker responses in both patients. CONCLUSIONS: A novel homozygous GRK1 mutation (p.P391H) was found in 2 Japanese siblings with Oguchi disease. Visual function in the 2 patients has not deteriorated with age, indicating that the disease is stationary. This is the first report of any patient with GRK1-associated Oguchi disease with markedly reduced cone responses.

Adult↗
PubMed2006

Compound heterozygous RDH5 mutations in familial fleck retina with night blindness.

PURPOSE: To describe the clinical features and genetic analysis of a 3-year-old boy diagnosed with familial fleck retina with night blindness. METHODS: The proband and his parents and grandparents were included. History, visual acuity and fundus examinations were evaluated. Bright-flash (rod-plus-cone) electroretinograms (ERGs) were recorded after 30 mins and 180 mins of dark adaptation. Mutation screening of the RDH5 gene encoding 11-cis retinol dehydrogenase was performed. RESULTS: The parents noticed the proband's night blindness when he was 2 years old. Best corrected visual acuity was 1.0 in both eyes. Fundus examinations revealed numerous yellow-white flecks of varying size and shape throughout the midperipheral to far peripheral retina in both eyes. The distribution, size and shape of the flecks were comparable to those seen in familial fleck retina with night blindness, rather than fundus albipunctatus. The ERGs showed extremely diminished responses after 30 mins of dark adaptation, but there were substantial increases in the amplitudes of both a- and b-waves when recorded after 180 mins of dark adaptation. Although a total of 19 RDH5 mutations have been found only in patients with fundus albipunctatus, compound heterozygous mutations, p.V177G and p.L310delinsEV, whose combination has not been previously reported, were found in the proband. The asymptomatic parents and one of the grandparents each carried one of the mutations, consistent with autosomal recessive transmission. CONCLUSION: Our study indicates that different mutations in the RDH5 gene can cause phenotypic variations of either fundus albipunctatus or familial fleck retina with night blindness.

Alcohol Oxidoreductases↗
PubMed2005

Novel NR2E3 mutations (R104Q, R334G) associated with a mild form of enhanced S-cone syndrome demonstrate compound heterozygosity.

PURPOSE: We investigated the ophthalmic features of a mild form of enhanced S-cone syndrome (ESCS) in a 33-year-old Japanese female proband and 3 unaffected family members. A genetic analysis was performed. DESIGN: Genetic and observational case study. METHODS: Fundus examinations, optical coherence tomography (OCT), Goldmann visual field (VF) perimetry, color vision tests, spectral sensitivity, and full-field and spectral electroretinography (ERG) were performed. Mutation screening of the NR2E3 gene, which encodes a photoreceptor-specific orphan nuclear receptor, was performed with polymerase chain reaction amplification and direct sequencing. MAIN OUTCOME MEASURES: Mutations in the NR2E3 gene, fundus photographs, OCT images, VFs, spectral sensitivity, and ERG findings. RESULTS: The diagnosis of ESCS was made based on the distinctive spectral ERG findings: hypersensitivity to blue stimuli and hyposensitivity to red stimuli. The proband had good visual acuity, normal color vision, good central VFs, and nearly normal spectral sensitivity. Funduscopy showed degenerative lesions in the vascular arcades to the midperipheral retina. The OCT images showed a morphologically normal macular thickness. In the full-field ERG, low amplitudes of rod b-waves were detected. Waveforms between rod-plus-cone and cone ERGs were very similar. Mutation analysis identified 2 novel compound heterozygous missense mutations, p.R104Q and p.R334G, which reside in the DNA-binding domain (DBD) and ligand-binding domain (LBD), respectively. The unaffected parents carried one of these mutations each, consistent with autosomal recessive transmission. CONCLUSIONS: Our study suggests that the expression of these 2 mutants of NR2E3, acting as a dimer, is correlated with a mild form of ESCS in that full foveal function and retinal laminar structure are maintained, and certain rod responses are present. This may be explained by the possibility that the heterodimers encoded by the 2 mutant alleles retain certain NR2E3 functions through the respective intact DBD and LBD.

Adult↗
PubMed2005

CYP4V2 mutations in two Japanese patients with Bietti's crystalline dystrophy.

Bietti's crystalline dystrophy (BCD) is an autosomal-recessive retinal dystrophy characterized by numerous glistening intraretinal dots scattered over the fundus, particularly in the posterior pole. The purpose of this study was to report mutations in the CYP4V2 gene (encoding a ubiquitously-expressed 525-amino acid sequence belonging to the CYP450 family) and to investigate the impact of the mutation on pre-mRNA splicing. DNA and RNA analyses were conducted using blood samples from two unrelated Japanese patients with BCD (a 46-year-old female and a 52-year-old male). In the female patient, a homozygous deletion/insertion mutation (g.IVS6-8_-1delc.802_810del/insGC) including the 3 -acceptor splice site was identified. Reverse transcription-PCR analysis revealed that the complete length of exon 7 (186 bp), is skipped, resulting in the in-frame deletion mutation (p.V268_E329del). Conversely, the male patient was a compound heterozygote for the deletion/insertion and novel nonsense (p.W340X) mutations. Clinically, the female patient had decreased visual acuity, constriction of visual fields, severely reduced amplitudes in both rod and cone electroretinograms (ERGs). Despite being 6 years older, the male patient presented with milder clinical manifestations having good visual acuity and substantial amplitudes in both rod and cone ERGs. Because the CYP4V2 truncated protein with the p.W340X mutation lacks 186 amino acids at the C-terminus, if expressed, it retains 62 amino acids encoded in exon 7, which are important for enzymatic activity. In the male patient, expression of both mutant alleles may compensate for the malfunction of each mutated protein and could explain why a milder form of BCD results from compound heterozygosity.

Cytochrome P-450 Enzyme System↗
PubMed2005

Dominant optic atrophy caused by a novel OPA1 splice site mutation (IVS20+1G-->A) associated with intron retention.

Dominant optic atrophy (DOA) is the most common form of inherited primary optic neuropathy. The purpose of the current study was to report a novel OPA1 splice site mutation and investigate the impact of the mutation on pre-mRNA splicing in a female proband and her father diagnosed with DOA. We evaluated visual acuity, retinal fundi and kinetic visual fields. Color vision phenotypes were determined using the Farnsworth Panel D-15 and the Farnsworth-Munsell 100-hue tests. All 28 coding exons of the OPA1 gene were analyzed with polymerase chain reaction (PCR) amplification and direct sequencing. Total RNA extraction from white blood cells followed by reverse transcription-PCR (RT-PCR) was performed. We identified a novel heterozygous G to A mutation at position +1 of intron 20 (g.IVS20+1G-->A) in both patients. RT-PCR analysis revealed that the first 25 bp from intron 20 plus exon 20 were spliced onto exon 21. No difference in expression of mutant and wild-type transcripts was found within the linear range of amplification. Clinically, both patients exhibited reduced visual acuities, pallor of optic discs, decreased sensitivities of central visual fields and blue-yellow color vision defects. Previously, only one mechanism (skipping of exon) of pre-mRNA splicing defects has been reported among OPA1 splice site mutations. Our study demonstrates that the mechanism of intron retention is a novel type of pre-mRNA splicing defects. The mutant transcript with a premature termination codon is likely to encode a truncated protein, due to a translational frameshift (V672fsX675), that lacks 289 amino acids of the C-terminal end. Therefore, it is suggested that haploinsufficiency underlies DOA in the patients. However, we could not exclude the possibility that the truncated protein has a dominant negative activity because the mutant transcript is insusceptible to nonsense-mediated mRNA decay.

Adult↗
PubMed2005

Lipid peroxidation during ischemia depends on ischemia time in warm ischemia and reperfusion of rat liver.

Prolonged hepatic warm ischemia has been incriminated in oxidative stress after reperfusion. However, the magnitude of oxidative stress during ischemia has been controversial. The aims of the present study were to elucidate whether lipid peroxidation progressed during ischemia and to clarify whether oxidative stress during ischemia aggravated the oxidative damage after reperfusion. Rats were subjected to 30 to 120 min of 70% warm ischemia alone or followed by reperfusion for 60 min. Lipid peroxidation (LPO) was evaluated by amounts of phosphatidylcholine hydroperoxide (PC-OOH) and phosphatidylethanolamine hydroperoxide (PE-OOH) as primary LPO products. Total amounts of malondialdehyde and 4-hydroxy-2-nonenal (MDA + 4-HNE), degraded from hydroperoxides, were also determined. PC-OOH and PE-OOH significantly increased at 60 and 120 min ischemia with concomitant increase of oxidized glutathione. These hydroperoxides did not increase at 60 min reperfusion after 60 min ischemia, whereas they did increase at 60 min reperfusion after 120 min ischemia with deactivation of phospholipid hydroperoxide glutathione peroxidase and superoxide dismutase. The amount of MDA + 4-HNE exhibited similar changes, but the velocity of production dropped with ischemic time longer than 60 min. In conclusion, oxidative stress progressed during ischemia and triggered the oxidative injury after reperfusion. Secondary LPO products are less sensitive, especially during ischemia, which may cause possible underestimation and discrepancy.

Aldehydes↗
PubMed2004

Rapid formation of 4-hydroxy-2-nonenal, malondialdehyde, and phosphatidylcholine aldehyde from phospholipid hydroperoxide by hemoproteins.

4-Hydroxy-2-nonenal (HNE) and malondialdehyde (MDA) are well-known toxic products of lipid peroxidation. Phosphatidylcholine aldehydes are also known as oxidation products of phosphatidylcholine. The mechanism of the formation of these compounds in vivo has been a long-standing question. We observed that the rapid reaction of hemoproteins (methemoglobin, metmyoglobin, and cytochrome c) with 1-palmitoyl-2-(13-hydroperoxy-cis-9, trans-11-octadecadienoyl) phosphatidylcholine (PLPC-OOH), having a hydroperoxylinoleoyl residue, generated HNE, MDA, and the phosphatidylcholine aldehyde 1-palmitoyl-2-(9-oxononanoyl) phosphatidylcholine. The efficiencies (mol% yield) of the formation of HNE and MDA from decomposed PLPC-OOH by methemoglobin, metmyoglobin, and cytochrome c after incubation for 10 min were 1.6, 1.0, and 1.0% for HNE and 1.2, 0.6, and 0.9% for MDA, respectively. When 1-palmitoyl-2-linoleoyl phosphatidylcholine was incubated with lipoxidase and methemoglobin, the formation of HNE and the phosphatidylcholine aldehyde 1-palmitoyl-2-(9-oxononanoyl) phosphatidylcholine was observed. When 1-palmitoyl-2-arachidonyl phosphatidylcholine was used instead of 1-palmitoyl-2-linoleoyl phosphatidylcholine, the phosphatidylcholine aldehyde 1-palmitoyl-2-oxovaleroyl phosphatidylcholine was obtained. These data suggest that HNE and phosphatidylcholine aldehydes might be rapidly formed from phosphatidylcholine by lipoxygenase and hemoproteins. Furthermore, hemichrome, converted from methemoglobin by deoxycholic acid and ursodeoxycholic acid, showed marked decomposition of HNE. These results suggest that hemoproteins are related to both the formation and the decomposition of HNE.

Aldehydes↗
PubMed2004

X-linked high myopia associated with cone dysfunction.

OBJECTIVE: Bornholm eye disease (BED) consists of X-linked high myopia, high cylinder, optic nerve hypoplasia, reduced electroretinographic flicker with abnormal photopic responses, and deuteranopia. The disease maps to chromosome Xq28 and is the first designated high-grade myopia locus (MYP1). We studied a second family from Minnesota with a similar X-linked phenotype, also of Danish descent. All affected males had protanopia instead of deuteranopia. METHODS: X chromosome genotyping, fine-point mapping, and haplotype analysis of the DNA from 22 Minnesota family individuals (8 affected males and 5 carrier females) and 6 members of the original family with BED were performed. Haplotype comparisons and mutation screening of the red-green cone pigment gene array were performed on DNA from both kindreds. RESULTS: Significant maximum logarithm of odds scores of 3.38 and 3.11 at theta = 0.0 were obtained with polymorphic microsatellite markers DXS8106 and DXYS154, respectively, in the Minnesota family. Haplotype analysis defined an interval of 34.4 cM at chromosome Xq27.3-Xq28. Affected males had a red-green pigment hybrid gene consistent with protanopia. We genotyped Xq27-28 polymorphic markers of the family with BED, and narrowed the critical interval to 6.8 cM. The haplotypes of the affected individuals were different from those of the Minnesota pedigree. Bornholm eye disease-affected individuals showed the presence of a green-red hybrid gene consistent with deuteranopia. CONCLUSIONS: Because of the close geographic origin of the 2 families, we expected affected individuals to have the same haplotype in the vicinity of the same mutation. Mapping studies, however, suggested independent mutations of the same gene. The red-green and green-red hybrid genes are common X-linked color vision defects, and thus are unrelated to the high myopia and other eye abnormalities in these 2 families. CLINICAL RELEVANCE: X-linked high myopia with possible cone dysfunction has been mapped to chromosome Xq28 with intervals of 34.4 and 6.8 centimorgan for 2 families of Danish origin.

Adolescent↗
PubMed2004

Four Japanese male patients with juvenile retinoschisis: only three have mutations in the RS1 gene.

PURPOSE: To describe the clinical phenotypes of four unrelated Japanese male patients with juvenile retinoschisis and to investigate occurrences of mutations in the RS1 gene. DESIGN: Observational case series and experimental study. METHODS: Fundus examinations, fluorescein angiography, and single-flash electroretinography (ERG) were carried out. In one patient, optical coherence tomography (OCT) was performed. The coding regions of the RS1 gene that encodes retinoschisin were amplified by polymerase chain reaction (PCR). The PCR products were purified and directly sequenced. RESULTS: The four affected patients showed cystoid- or wheel-like foveal changes with a little or no fluorescein leakage and negative b-wave patterns in both eyes. The OCT images of foveal retinoschisis disclosed that splitting occurs in the putative fibers of Henle. In three patients, we identified three different missense mutations (p.S73P, p.Y89C, p.R209C) in the functionally important discoidin domain of the RS1 gene. The p.S73P mutation has not been previously reported. In contrast, no nucleotide substitutions were detected in the fourth patient whose parents were unrelated and asymptomatic. No other member of this family for three generations has had juvenile retinoschisis. CONCLUSION: Because serine 73 is conserved in the mouse ortholog and other discoidin proteins, the proline 73 allele is therefore very likely to encode a defective retinoschisin. Although the inheritance pattern is uncertain in the patient without the RS1 mutation, the clinical and ERG findings were indistinguishable from those of patients with RS1 mutations. This finding points to the genetic heterogeneity of juvenile retinoschisis.

Adolescent↗
PubMed2004

Autosomal dominant familial exudative vitreoretinopathy in two Japanese families with FZD4 mutations (H69Y and C181R).

BACKGROUND: Familial exudative vitreoretinopathy (FEVR) is a hereditary disorder characterized by impaired vascularization of parts of the peripheral retina. Autosomal dominant FEVR (adFEVR), a major form of FEVR and assigned to chromosome 11q13-23 (EVR1) locus, is caused by deletion mutations in the C- terminal region of the frizzled-4 (FZD4) gene. This paper describes the clinical phenotype of adFEVR in two Japanese families with two different mutations in the FZD4 gene. METHODS: We encountered three Japanese patients with adFEVR and studied them using mutation analysis of the FZD4 gene with PCR, sequencing, and a restriction enzyme digestion. RESULTS: Two previously unreported missense mutations, p.H69Y and p.C181R, were identified in the N-terminal extra- cellular region of two of the patients. This region was highly conserved among other vertebrate species and FZD family members, unlike the C-terminal region. Co-segregation analysis revealed that all affected individuals carried one of these mutations, while unaffected individuals did not. The mutations were not detected in normal individuals (n=120). The affected individuals had mild to severe retinal abnormalities. CONCLUSIONS: FZD4 mutations in either the N- or C-terminal region underlie adFEVR, which indicates that FZD4 plays an important role in retinal angiogenesis. Analysis of FZD4 mutations in families with adFEVR is useful for genetic counseling and for early diagnosis

Amino Acid Sequence↗
PubMed2004

Enhanced S-cone syndrome in a Japanese family with a nonsense NR2E3 mutation (Q350X).

PURPOSE: To describe the clinical characteristics of a Japanese male patient with enhanced S-cone syndrome (ESCS) and investigate the existence of mutations in the NR2E3 gene, which encodes a photoreceptor cell-specific nuclear receptor. METHODS: Fundus examinations, fluorescein angiography, colour vision tests, spectral sensitivity, and full-field and spectral electroretinography were performed. Mutation screening of the NR2E3 gene was performed with polymerase chain reaction (PCR) amplification and direct sequencing. RESULTS: We identified a novel homozygous mutation (c.1048C > T), that converts glutamine (CAA) to a termination codon (TAA) at amino acid position 350. The subject's unaffected parents were heterozygous for the mutation, consistent with autosomal recessive transmission. The electroretinographic findings revealed that the patient had neither rod nor 30-Hz flicker responses but did have cone responses with large a-wave and low b-wave amplitudes, similar to the rod-plus-cone responses, and also substantial short wavelength-sensitive (S) cone and extremely diminished long/middle wavelength-sensitive (L/M) cone responses. In the right eye, spectral sensitivity in the fovea revealed both functional S-cone and remarkably reduced L- and M-cone sensitivities, which was compatible with the decreased visual acuity (VA) and red/green colour vision defects noted in this eye. In contrast, the patient had good VA and normal red/green colour vision in the left eye. CONCLUSION: The nonsense mutation results in a truncated NR2E3 protein lacking 61 amino acids within the ligand-binding domain (LBD) that consists of 190 amino acids of the C-terminus end. Therefore, null function of the LBD is likely to cause ESCS in the patient. The clinical findings for this patient suggest that his left eye, with its functional L/M- and S-cones, was at an earlier stage of the syndrome than his right eye.

Adolescent↗
PubMed2004

[A protanomalous female whose genotype of red/green visual pigment genes was determined by molecular analysis of her family members].

PURPOSE: To determine X-linked red/green visual pigment gene arrays of a female proband with protan deficiency. METHODS: We examined a brother and both parents as well as the proband. Severity, severe or mild form, of color vision deficiency was estimated with either failure or passing of the Farnsworth Panel D-15 test. Diagnosis of either anomalous trichromacy or dichromacy was performed using a Nagel Type I anomaloscope. Genotypes of red/green visual pigment genes were determined by quantitative polymerase chain reaction-single strand conformation polymorphism analysis. RESULTS: Color vision tests revealed that the proband, her brother, her father, and her mother had protanomaly(mild form), protanopia, protanomaly(severe form), and normal color vision, respectively. In analysis of gene arrays, the brother had a red-green hybrid gene(R1G2, Ser 180) and three green visual pigment genes, while the father had a red-green hybrid gene(R4G5, Ser 180) and a green visual pigment gene. CONCLUSIONS: It is impossible to directly determine each paternal or maternal X-linked red/green pigment gene array in the female proband. Molecular analysis of the family members revealed that the proband was a compound heterozygote for two R1 G2 and R4G5 hybrid genes encoding photopigments with different absorption maxima.

Chromosomes, Human, X↗
PubMed2002

A comparative study on the hydroperoxide and thiol specificity of the glutathione peroxidase family and selenoprotein P.

Glutathione peroxidase catalyzes the reduction of hydrogen peroxide and organic hydroperoxide by glutathione and functions in the protection of cells against oxidative damage. Glutathione peroxidase exists in several forms that differ in their primary structure and localization. We have also shown that selenoprotein P exhibits a glutathione peroxidase-like activity (Saito, Y., Hayashi, T., Tanaka, A., Watanabe, Y., Suzuki, M., Saito, E., and Takahashi, K. (1999) J. Biol. Chem. 274, 2866-2871). To understand the physiological significance of the diversity among these enzymes, a comparative study on the peroxide substrate specificity of three types of ubiquitous glutathione peroxidase (cellular glutathione peroxidase, phospholipid hydroperoxide glutathione peroxidase, and extracellular glutathione peroxidase) and of selenoprotein P purified from human origins was done. The specific activities and kinetic parameters against two hydroperoxides (hydrogen peroxide and phosphatidylcholine hydroperoxide) were determined. We next examined the thiol specificity and found that thioredoxin is the preferred electron donor for selenoprotein P. These four enzymes exhibit different peroxide and thiol specificities and collaborate to protect biological molecules from oxidative stress both inside and outside the cells.

Glutathione Peroxidase↗
PubMed2002

The molecular basis of dichromatic color vision in males with multiple red and green visual pigment genes.

We investigated the genotypic variation in 50 red-green color vision deficient males (27 deuteranopes and 23 protanopes) of middle European ancestry who possess multiple genes in the X-linked photopigment gene array. We have previously shown that only the first two genes of the array are expressed and contribute to the color vision phenotype. Therefore, the hypothesis is that the first two genes possessed by multigene-dichromats encode pigments of identical or nearly identical spectral sensitivity: one gene normal (R or G) and the other a hybrid (G/R or R/G). The spectral sensitivities of the encoded pigments were inferred from published in vitro and in vivo data. The color vision phenotype was assessed by standard anomaloscopy. Most genotypes (92%) included hybrid genes whose sequence and position and whose encoded pigment correlated exactly with the phenotype. However, one and possibly two of the protanopes had gene arrays consistent with protanomaly rather than protanopia, since two spectrally different pigments may be encoded by their arrays. Two of the deuteranopes had only R- and G-photopigment genes, without any detectable G/R-hybrid genes or any as-of-yet identified point mutation or coding/promoter sequence deletions. Further, an unexpectedly high number of multigene-deuteranopes (11%) had the C203R mutation in their most upstream G-pigment gene, suggesting a founder effect of middle European origin for this mutation. About half of the protanopes possessed an upstream R/G-hybrid gene with different exon 2 coding sequences than their downstream G-pigment gene(s), which is inconsistent with published data implying that a single amino acid substitution in exon 2 can confer red-green color discrimination capacity on multigene-protans by altering the optical density of the cones.

Color Perception↗
PubMed2002

Paraquat- and diquat-induced oxygen radical generation and lipid peroxidation in rat brain microsomes.

NADPH-menadione reductase activity by rat brain microsomes (Ms) was decreased 40-50% by 10 microM dicumarol, a potent inhibitor of DT-diaphorase, whereas no change in NADPH-paraquat (PQ) and -diquat (DQ) reductase activity was observed. NADPH-DQ reductase activity in brain Ms was 2.5-fold higher than NADPH-PQ reductase activity. The formation of PQ and DQ radicals was verified optically and observed directly by ESR spectroscopy in the NADPH-PQ and -DQ reductase reactions by brain Ms under anaerobic conditions. PQ- and DQ-induced superoxide formation was confirmed by the detection of DMPO-OOH ESR signals and followed by chemiluminescence (CL) of a Cypridina luciferin analogue (CLA). The kinetics and intensity of the CL were consistent with the observations that the reduction in DQ is faster than that in PQ. Thiobarbituric acid reactive substances (TBARS) and phospholipid hydroperoxides in brain Ms increased in the presence of NADPH and Fe3+. The generation of both lipid peroxidation products derived from brain Ms decreased with increasing concentrations of PQ and DQ. The inhibitory effect of DQ is more pronounced than that of PQ. The formation of PQ- and DQ-induced reactive oxygen species was not associated with lipid peroxidation in rat brain Ms.

Animals↗
PubMedDate not supplied

Expression of rinx/vsx1 during postnatal eye development in cone-bipolar, differentiating ganglion, and lens fiber cells.

PURPOSE: To investigate the expression pattern of the homeobox transcription factor Rinx (also referred to as Vsx1) during postnatal eye development of the mouse. METHODS: We cloned the mouse Rinx gene, inferred the sequence of the encoded protein, and prepared polyclonal antibodies against it. Immunohistochemical analysis (IHC) and in situ hybridization were employed to localize Rinx in postnatal and adult mouse eyes. Double-labeled IHC either with anti-protein kinase C (PKC, a marker of rod bipolar cells) or anti-vimentin (a marker of Muller glial cells) antibodies was performed in the adult retina. Rinx mRNA was also analyzed by reverse transcription-polymerase chain reaction in the lens. RESULTS: At P0 and P4 (postnatal days), Rinx-immunoreactive cells included retinal ganglion cells (RGC), cells of the innermost nuclear layer (INL) and of presumptive INL, differentiating lens fiber cells, and a few cells of the presumptive outer nuclear layer (ONL). At P8, both Rinx protein and mRNA were detected in the middle of the INL, and in RGC, but not in the lens. When the mice were 8 weeks of age, only a subset of nuclei in the outer half of the INL expressed both Rinx protein and mRNA. Double-labeling IHC indicated that Rinx- and either PKC- or vimentin-labeled cells were not colocalized. Therefore, Rinx is most likely expressed in adult cone bipolar cells and possibly in horizontal cells. CONCLUSIONS: Rinx may play important roles in the differentiation and maintenance of cone bipolar cells. Rinx is unique among members of this family of homeodomain proteins in that it may also be involved in differentiation of RGC and lens fiber cells.

Amino Acid Sequence↗
PubMedDate not supplied

Clinical heterogeneity between two Japanese siblings with congenital achromatopsia.

Congenital achromatopsia is a stationary retinal disorder with autosomal recessive inheritance. It is characterized by significant attenuation of cone-photoreceptor function. Symptoms include photophobia, nystagmus, and poor visual acuity from birth. Unlike in cone or cone-rod dystrophies, the retinal fundus usually appears normal. Here we describe two siblings with congenital achromatopsia, who exhibit different ophthalmic phenotypes. History was taken, and ophthalmic examinations were performed in a 7-year-old girl and her 5-year-old brother, who were referred to our department because of poor visual acuity. Two of their grandparents were brother and sister, suggesting an autosomal recessive transmission in inheritance. They have been followed for more than 13 years since the initial evaluation. Symptoms, visual acuity, and kinetic visual field were very similar to each other, consistent with findings of typical congenital achromatopsia. However, color-vision tests suggested that the brother had residual color discrimination, but the sister did not. The siblings had different full-field electroretinographic and spectral-sensitivity findings: residual cone functions were detected in only the brother, in agreement with his residual color vision. They also had different findings of retinal fundi and ocular refractions: the sister had bilaterally atrophic-appearing macular lesions and myopic errors. In contrast, the brother remains hyperopia and has exhibited no specific retinal findings until age 18 years. The causes why both complete and incomplete achromats occur in the siblings are uncertain but might be caused by modifying effects of sex-related genes or by environmental factors influencing certain gene regulations in cone photoreceptors.

Child↗