Progression of visual field defect in a normal-tension glaucoma patient after laser in situ keratomileusis.
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Adult↗
Biomedical subjects
M Wakakura
Publications and source records attributed to M Wakakura.
Etizolam and benzodiazepine induced blepharospasm.
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Adult↗
[Experimental approaches to prophylactic neuroprotective treatment for retinal and optic nerve disorders].
Neuroprotective treatment is increasingly recommended as a novel intervention for ischemic or degenerative disorders in the retina and optic nerve. To determine prophylactic neuroprotective action and the mechanism of various agents against N-methyl-D-aspartate NMDA- or L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced cell death, in vitro experiments were conducted on retinal neurons and Müller cells. The effects of a calcium channel blocker, diltiazem, and a dopamine precursor, L-dopa, on glutamate agonist exposure were investigated using the TdT-mediated dUTP-biotin nick end labelling (TUNEL) method and comet assay. Prior administration of either one of the above two agents showed that cell death was prevented following exposure to NMDA or AMPA. Isolated administration of L-dopa at a concentration of 10(-4) M facilitates cell death, probably because of nitric oxide (NO) production. L-dopa concentrations of less than 10(-6) M did not result in increased cell death, and glutamate agonist-induced cell death was significantly suppressed by prior treatment at these low concentrations. Similar induction and suppression of cell death was also shown in cultured Müller cells. Based on our experiments and other published literature, we looked at three hypotheses for possible mechanisms for the neuroprotection of L-dopa, i.e., interactions with dopamine receptors, the anti-apoptotic action of NO, and the actions of neurotrophic or nerve growth factors. Neuroprotection appeared to occur through the D1 or D2 receptors. From data obtained from video-enhanced microscopic recordings, which can be used to observe real-time intracellular movement of particles, the movement after administration of a D1 receptor agonist was found to be remarkably different than that seen after D2 agonist administration. It is suggested that the action of dopamine on retinal cell death should be analyzed separately with respect to D1 and D2 receptors. We also discuss clinical application of these two agents in retinal and optic nerve ischemia.
Animals↗
Corneal amyloidosis complicated by trichiasis. Immunohistochemical identification of the amyloid light chain protein
Purpose: To identify the amyloid protein of the corneal amyloidosis complicated by trichiasis.Methods: The two patients were 41-year-old and 38-year-old women with trichiasis. They had gelatinous drop-like corneal change in the hemilateral eye. The lesion was excised and examined by light and electron microscopy. Additionally, we performed an immunohistochemical study with immunofluorescence techniques using cryosections.Results: The amyloid deposits were confirmed with light and electron microscopy. Congo red positive staining was not reduced following pretreatment with potassium permanganate. Immunohistochemically, amyloid deposits in the cornea stained positively with serum human light chain kappa and lambda. Pretreatment of the section with 0.05% Tween-20 did not decrease the staining with fluorescence. The deposits stained negatively with serum prealbumin and keratin antibodies.Conclusions: These findings indicate the protein of the corneal amyloidosis complicating trichiasis to be an amyloid light chain (AL) protein that has never been identified in this kind of corneal amyloidosis.
Journal Article↗
Do idebenone and vitamin therapy shorten the time to achieve visual recovery in Leber hereditary optic neuropathy?
OBJECTIVES: The authors investigated the effectiveness of idebenone combined with vitamin B2 and vitamin C in the treatment of patients with Leber hereditary optic neuropathy (LHON) in an early stage as compared with untreated patients with LHON. These agents may stimulate the formation of ATP. MATERIALS AND METHODS: For this retrospective study, the authors selected 28 outpatients with LHON from the Keio University Hospital. These patients were followed for 2 to 19 years from disease onset. They were divided into two groups: 14 untreated patients (11778 mutation in 10 patients, 3460 mutation in 2 patients, and 14484 mutation in 2 two patients); and 14 treated patients (11778 mutation in 11 patients, 3460 mutation in 1 patient, and 14484 mutation in 2 patients). The treated patients were administered medical treatment with idebenone, vitamin B2, and vitamin C for at least 1 year. The current study evaluated the following: 1) number of eyes with visual recovery > or = 0.3; 2) interval between the onset of LHON and the beginning of visual recovery; 3) interval between the onset of LHON and visual recovery to 0.3; and 4) interval between the beginning of medical treatment and the beginning of visual recovery in the treated subjects. RESULTS: There was no significant difference in the number of eyes with visual recovery > or = 0.3 in the two groups with the 3460, 11778, or 14484 mutation. Patients with visual recovery showed a fenestrated scotoma or a clearing of central vision. The mean interval between the onset of LHON and the beginning of visual recovery was significantly shorter in the treated group (11.1 months) than in the untreated group (17.4 months) (P = 0.03). The mean interval between the onset of LHON and visual recovery to 0.3 was significantly shorter in the treated group (17.6 months) than in the untreated group (34.4 months) (P = 0.01). The mean interval between the initiation of medical treatment to the beginning of visual recovery was 5.4 months. CONCLUSIONS: Results suggest that the administration of idebenone, vitamin B2, and vitamin C sped the recovery of vision in patients with LHON.
Adolescent↗
[Corneal amyloidosis complicated by trichiasis--immunohistochemical identification of the amyloid light chain protein].
PURPOSE: To identify the amyloid protein of the corneal amyloidosis complicated by trichiasis. METHODS: The two patients were 41-year-old and 38-year-old women with trichiasis. They had gelatinous drop-like corneal change in hemilateral eye. The lesion was excised and examined by light and electron microscopy. Additionally, we performed an immunohistochemical study with immunofluorescence techniques using cryosections. RESULTS: The amyloid deposits were confirmed with light and electron microscopy. Congo red positive staining was not reduced following pretreatment with potassium permanganate. Immunohistochemically, amyloid deposits in the cornea stained positively with serum human light chain kappa and lambda. Pretreatment of the section with 0.05% Tween-20 did not decrease the staining with fluorescence. The deposits stained negatively with serum prealbumin and keratin antibodies. CONCLUSIONS: These findings indicate the protein of the corneal amyloidosis complicating trichiasis to be an amyloid light chain (AL) protein that has never been identified in this kind of corneal amyloidosis.
Adult↗
Rapid increase in cytosolic calcium ion concentration mediated by acetylcholine receptors in cultured retinal neurons and Müller cells.
PURPOSE: This study was conducted to detect the presence of muscarinic or nicotinic receptors in cultured retinal neurons and Müller cells. METHODS: Pure Müller cell cultures and cocultures of retinal neurons and Müller cells were used; the former, obtained from adult rabbit retinas, and the latter, retinal neurons from neonatal rats, were cocultured with Müller cells. Intracellular calcium ion concentration ([Ca2+]i) following the administration of acetylcholine, a cholinesterase inhibitor (trichlorfon), nicotine or muscarinic agonist with or without a receptor antagonist was monitored using the calcium ion indicator, fura-2. RESULTS: Acetylcholine and trichlorfon induced rapid increase in [Ca2+]i in half of either cell type. Trichlorfon induced positive response in coculture but not in the pure Müller cell cultures. This positive response was blocked only partially in the presence of atropine. Approximately 30-40% of neurons responded to nicotine at 5 microM, which was significantly blocked by alpha-bungarotoxin at 50 nM. No response to nicotine could be detected in Müller cells. Approximately 50% of neurons responded to muscarine at 50 microM, but 500 microM was required for the formation of calcium transients in 50% of Müller cells. The muscarine inducement of rapid increase in [Ca2+]i was blocked by atropine. The agonist of M1 (a muscarinic receptor subtype), McN-A-343, at 0.5 microM induced the most significant and rapid increase in [Ca2+]i both in neurons and Müller cells. McN-A-343 administration at 0.05 microM induced positive response in half the neurons, but only in approximately 10% of Müller cells. Such positive response was not observed following preincubation with the M1 antagonist, pirenzepine, at 50 microM. CONCLUSIONS: Cocultured retinal neurons enhance the release of acetylcholine following anticholinesterase administration, and approximately half the neurons were found to possess muscarinic and nicotinic receptors. However, Müller cells appeared to possess only the less sensitive muscarinic receptor. Muscarinic receptor subtypes on either type of cell contained at least M1.
Acetylcholine↗
Spectrum of pathogenic mitochondrial DNA mutations and clinical features in Japanese families with Leber's hereditary optic neuropathy.
PURPOSE: To investigate the incidence and clinical significance of primary or proposed secondary mitochondrial DNA (mtDNA) mutations in Japanese patients with Leber's hereditary optic neuropathy (LHON). METHODS: Blood samples from the 80 unrelated Japanese patients with bilateral optic atrophy were screened for primary LHON mutations. Patients found to have a primary LHON mutation were then tested for 9 proposed secondary LHON mutations. We investigated the association between these mutations and clinical characteristics. RESULTS: Primary mtDNA mutations were identified in 68 patients: at np 3460 in 3 (4%) of 68 patients, at np 11,778 in 59 patients (87%), and at np 14,484 in 6 patients (9%). We identified 5 secondary mtDNA mutations (at np 3394, 4216, 7444, 9438 or 13,708) in 10 (15%) of 68 LHON patients and 3 mutations (at np 3394, 4216 or 3708) in 6 (7%) of 90 healthy Japanese individuals. No patient was positive for more than one secondary mutation. The frequency of secondary mutations was similar in the 68 LHON patients and 90 controls. The clinical features of the Japanese patients with any of the 3 primary LHON mutations were similar to those of Caucasian patients, despite different mtDNA backgrounds in these populations. The percentage of patients with familial LHON harboring the 3460 or 14,484 mutations was lower in the Japanese population. CONCLUSIONS: Japanese patients with LHON exhibited a very high incidence (87%) of the 11,778 primary mutation. Most of the proposed secondary LHON mutations were rare in the Japanese population and they, except the 7444 mutation, may not influence the clinical features of LHON.
Adolescent↗
[Orbital and stomach metastasis from invasive lobular breast carcinoma].
Orbital or ocular metastatic tumors may originate from breast cancer. Few studies have been made regarding their histopathological classification. A 71-year-old female noted a tumor in the right orbital region. She had had bilateral breast cancer 2 years before and gastric cancer 5 months before. Histopathology had shown stage II invasive ductal cancer (scirrhus) in the right breast and stage III invasive lobular cancer in the left. Signet-ring cells were present in the breast and gastric cancers. Biopsy of the right lower eyelid showed poorly differentiated adenocarcinoma with signet-ring cells. Indian file pattern, which is specific for invasive lobular cancer, was also present, suggesting that the orbital tumor had metastatized from the left breast cancer. Genetic analysis of the gastric cancer using polymerase chain reaction showed a mutation at exon 8 of the p53 tumor suppressor gene, indicating the cancer to be metastatic. These results led to the conclusion that invasive lobular cancer of the left breast was the primary lesion for the gastric and orbital metastases. This case also illustrates that signet-ring cells, which are usually seen in gastric cancer, may be present in invasive lobular breast cancer and in orbital metastasis.
Aged↗
[Heat-shock proteins in the eye].
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Animals↗
[Central serous chorioretinopathy induced by corticosteroids].
Five patients were diagnosed as having central serous chorioretinopathy (CSC) during systemic corticosteroid treatment based on medical records and fluorescein angiography. Twenty-eight previously reported corticosteroid-induced CSC cases in addition to these 5 were examined to clarify clinical differences between idiopathic CSC and corticosteroid-induced CSC. Nine previously reported cases of corticosteroid-induced multifocal posterior pigment epitheliopathy (MPPE) were also reviewed. The corticosteroid-induced CSC patients were older and less male-dominant. In MPPE, bilateral involvement was noted in most cases and females were dominant. We found two patient groups; in the short latency group, the onset of CSC occurred within 70 days of corticosteroid administration and in the prolonged latency group, more than 6 months after. The daily dose of prednisolone for the former usually exceeded 20 mg/day, in contrast to the latter, at less than 20 mg/day. Immunosuppressive drugs such as cyclophosphamide made it possible to diminish the onset daily dose.
Adrenal Cortex Hormones↗
High incidence of visual recovery among four Japanese patients with Leber's hereditary optic neuropathy with the 14484 mutation.
The 14484 mutation in the ND6 gene of mitochondrial DNA (mtDNA) is a genetic mutation associated with Leber's hereditary optic neuropathy (LHON) in Caucasian patients who show a high incidence of visual recovery. We evaluated four Japanese patients with LHON associated with the 14484 mutation who were negative for eight proposed secondary mutations. There was no family history of optic atrophy in three of the four patients. All four patients were initially diagnosed as having optic neuritis, either anterior (Cases 1 and 3) or retrobulbar (Cases 2 and 4), based upon their fundus findings and clinical history. Molecular genetic testing of mtDNA confirmed the diagnosis of LHON in all four patients. The three patients who experienced recovery had their vision return to 20/50 or better in both eyes. The patient who did not was a heavy consumer of alcohol and tobacco. These findings indicate that Japanese patients with the 14484 mutation have a visual prognosis similar to that of Caucasians with this mutation.
Adolescent↗
[Application of oculokinetic perimetry in examination of the eye].
Oculokinetic perimetry was performed using the same protocol at four health screening facilities to determine its usefulness for identifying visual field abnormalities including glaucoma during complete physical screenings in Japan. Ophthalmoscopy of the optic disc, 26-point oculokinetic perimetry (OKP), and applanation tonometry were performed in 2,768 eyes. If any one of the tests yielded an abnormal result, the eye was then examined with a Humphrey visual field analyzer (HVFA, program 30-2). After the tests were completed, the results were evaluated by ophthalmologists for evidence of primary open-angle glaucoma and normal tension glaucoma and were classified into one of 3 groups: confirmed glaucoma, suspected glaucoma, and no glaucoma. OKP detected abnormalities in the visual field in 96 eyes (3.5%). Of these 96 eyes, 29 eyes had confirmed glaucoma, 52 eyes were suspected of having glaucoma and 15 eyes had no glaucoma. The remaining 15 eyes had no glaucoma, but in 7 of them other ophthalmological disease was diagnosed. The sensitivity, specificity, positive predictive value, and negative predictive value of OKP for detecting glaucomatous visual field defect were 0.46, 0.99, 0.84 and 0.96, respectively. The high specificity and negative predictive value show that OKP is unlikely to produce false positive results, but its low sensitivity suggests that it is not suitable for the early detection of glaucoma. However, OKP identified advanced glaucoma and other ophthalmological diseases associated with visual field abnormalities, suggesting that it is a useful screening test.
Adult↗
[Analysis of mutations and heteroplasmy at mitochondrial DNA 11778 using non-RI single strand conformation polymorphisms in Leber's hereditary optic neuropathy].
Leber's hereditary optic neuropathy(LHON) is a maternally inherited mitochondrial disease of an acute or subacute bilateral loss of central vision. G to A substitutions at nucleotide position 11778 in mitochondrial DNA(mt DNA) have been identified in approximately 40% to 90% of patients. In this study, regions containing mt DNA 11778 mutations were analyzed by polymerase chain reaction(PCR), non-RI single strand conformation polymorphisms(SSCP) and direct sequencing. In 26 visually affected patients, mt DNA 11778 mutations were detected in 9 patients (36.4%). In one pedigree of a LHON patient(L-6), four unaffected family members had heteroplasmy of the 11778 mutation using non-RI SSCP. Ratios of the heteroplasmy between wild type and mutant mt DNAs can be detected in non-RI SSCP and accurately quantified by video densitometric analyzer. Two types of novel polymorphisms, 11696 G to A and 11719 A to G, in the mt DNA region were also found in this non-RI SSCP analysis. Non-RI SSCP is an efficient and accurate method for diagnosis of mt DNA 11778 mutations and quantifying heteroplasmy in patients with LHON and pedigrees.
Base Sequence↗
Possible roles of AMPA/KA receptor in cultured Müller cells.
In order to identify the function of the AMPA/KA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate/kainate) receptor in cultured Müller cells, we studied the difference in the affinity of this receptor for cultured Müller cells and retinal neurons (neurons), comparing these to the characteristics of cultured Müller cells exposed to kainate (KA), a neurotoxic amino acid. The difference in the cellular responses of Müller cells and neurons to AMPA was evaluated by measuring the rapid change in intracellular calcium ions. Results showed that neurons were more sensitive to AMPA than Müller cells; the percentage of cells responding to AMPA was always higher for neurons. When Müller cells were exposed to 0.5 mM KA, the morphology of the cells was not affected and the concentration of lactate dehydrogenase in the culture solution did not increase. However, the percentage of cells responding to a high concentration of AMPA was higher in the Müller cells exposed to KA than in those not exposed. These findings indicated that the affinity of the AMPA receptor was lower in Müller cells than in neurons, and that Müller cells were resistant to neurotoxic amino acids. It was also suggested that when an extremely large amount of neurotoxic amino acid was released into the retina as a result of ischemia, Müller cells actively protected the neurons.
Animals↗
Leber's hereditary optic neuropathy among Japanese.
This article reviews the literature on point mutation of mitochondrial DNA (mtDNA) among Japanese and the authors' research data on pupil reaction in patients with Leber's hereditary optic neuropathy (LHON). Among Japanese, a higher frequency (80-90%) of point mutation at nucleotide position 11778 of mtDNA was found; other point mutations found were at nucleotide positions 3460, 14484, 13708, 7444, and 3394. Although pupil reaction to light stimulus is usually defective in all types of optic neuropathy, in patients with LHON the reaction was well maintained even when vision was reduced. W cells in the retina may be preserved or less damaged, even when the degenerative process progresses in both X and Y cells. Possible treatment is also described.
Adult↗
Evidence for preserved direct pupillary light response in Leber's hereditary optic neuropathy.
AIMS/BACKGROUND: Pupillary light response is usually defective in all types of optic neuropathy. However, the authors have observed in patients with Leber's hereditary optic neuropathy (LHON) relatively normal light response, with consequent misdiagnosis psychogenic visual loss in some cases. To confirm this clinical impression, afferent pupillary defect was assessed by measurement of adjusted constriction amplitude (CA) and escape rate (ER) by infrared videopupillography (Iriscorder-C 2515). METHODS: Thirteen consecutive patients (26 eyes) with LHON (average age 27.2 years) were examined; 12 had the mitochondrial DNA 11778 mutation and one the 14484 mutation. Seven of these patients had a positive family history. For comparison, the above rates were determined in 19 patients (23 eyes) with idiopathic optic neuritis (ON; average age 35.1 years), 18 patients (19 eyes) with anterior ischaemic optic neuropathy (AION; average age 58.1 years), and 25 volunteers (50 eyes) with healthy eyes (average age 39.6 years). RESULTS: The distribution of visual acuity was essentially the same in all optic neuropathy groups. Reduction in CA and increase in ER were significant in patients with ON and AION, but not in those with LHON. Only slight afferent pupillary defect was evident even 2 years after the onset of LHON. CA in AION and ER in ON were correlated statistically with visual acuity and Humphrey mean threshold deviation, while CA and ER in LHON were not. CONCLUSION: Pupillary light response in patients with LHON obviously differs from that in patients with other types of optic neuropathy. LHON appears to be pathophysiologically characterised by well preserved afferent fibres for pupillary light response (probably from W cells). Besides being of pathogenetic interest, the detection of clinical features should facilitate the diagnosis of LHON particularly when family history provides no indication.
Adult↗
Quantitative determination of heteroplasmy in Leber's hereditary optic neuropathy by single-strand conformation polymorphism.
PURPOSE: The maternal inheritance of Leber's hereditary optic neuropathy (LHON) is caused by defects in the genes of mitochondrial DNA (mtDNA). The most prevalent mtDNA mutation, present in 40% to 90% of families with this disease, is a G to A substitution at nucleotide position 11778. The rapid and accurate quantification of heteroplasmy of this mutation will help determine the relative risk for disease expression. METHODS: The authors conducted screening tests for heteroplasmy in 44 visually affected patients with the 11778 mutation and 34 unaffected members of 36 Japanese families with LHON using the single-strand conformation polymorphism analysis. This method can detect even a single base difference between the sequences of wild type and mutant DNA strands. The percentage of mutant mtDNA was calculated using an image analyzer. RESULTS: Single-strand conformation polymorphism analysis allowed the detection of heteroplasmy ranging from 5% to 95%. Five (14%) of the 36 families showed heteroplasmy, and 14 (18%) of the 78 persons tested had heteroplasmy ranging from 10% to 94%. Seven patients with heteroplasmy with visual loss had mutant mtDNA ranging from 62% to 94%. CONCLUSIONS: Single-strand conformation polymorphism analysis is rapid, efficient, and accurate for detecting point mutations and quantifying heteroplasmy in mtDNA. Individuals with heteroplasmy with less than 60% of mutant mtDNA in circulating leukocytes are probably at lesser risk for developing optic atrophy.
Adult↗