A Case of Congenital Idiopathic Enlargement of Extraocular Muscles.

The purpose of this case report is to report a case of congenital idiopathic enlargement of extraocular muscles. A four-month-old girl showed limitation of adduction and supraduction in the right eye. A computerized axial tomography (CAT) scan revealed hypertrophy of the lateral rectus muscle and inferior rectus muscle of the right eye. Thyroid hormone and antibody levels were normal. No inflammatory findings on magnetic resonance imaging (MRI). A traction test under general anesthesia revealed a strong limitation of supraduction and a mild limitation of adduction. Therefore, the inferior rectus muscle was recessed 4.5 mm at the age of six months. A partial biopsy of the inferior rectus showed no inflammatory cell infiltration. After the first surgery, the patient's limitation of supraduction improved, but the limitation of adduction persisted. So, a 5 mm recession of the right lateral rectus muscle was added at one year and one month. However, the hypertropia of the sound eye became stronger after treatment of amblyopia. Because of the strong limitation of supraduction, tenotomy of the inferior rectus was performed at the age of six years. Postoperatively, no impairment of infraduction occurred, and the limitation of supraduction was mildly improved. Since the findings on MRI were not changed through our observation period, we concluded that the patient had idiopathic external ophthalmoplegia.

A Case of Strabismus Fixus With Extremely Long Axial Length Results in Improvement of Limitation of Abduction by the Yokoyama Procedure.

Acquired strabismus in high myopia is typically fixed in the positions of adduction and depression, with restrictions in both abduction and elevation. As a treatment for myopic strabismus fixus, the Yokoyama procedure is effective. We report a case of strabismus fixus with a long axial length (34 mm), in which abduction limitation was improved by the Yokoyama procedure with medial rectus recession. A 68-year-old woman was referred for strabismus fixus in her right eye. Her right eye was fixed in the positions of adduction and depression, with restrictions in both abduction and elevation. The axial length of her right eye was extremely long 33.97mm. Magnetic resonance imaging (MRI) showed that the posterior eyeball of her right eye had dislocated out of the superotemporal muscle cone, and she was diagnosed with strabismus fixus with high myopia. She underwent the Yokoyama procedure in her right eye, and medial rectus recession was performed at the same time because abduction limitations remained at the end of the Yokoyama procedure. After surgery, there was a small residual esotropia, but abduction beyond the midline was possible, and the patient's satisfaction was high. A combination of the Yokoyama procedure and medial rectus recession for a patient with myopic strabismus fixus with long axial length resulted in good improvement of ocular misalignment and limitation of abduction.

Early Detection and Treatment of Congenital Cataracts Using Fetal Ultrasound: A Case of a Newborn With a Family History of Congenital Cataracts.

This case study highlights the advances in fetal ultrasonography, illustrating its role in early detection and management of congenital cataracts. We present the case of a male infant with a family history of congenital cataracts, where an in-utero ultrasound examination at 25 weeks of gestation revealed potential cataracts. His mother and brother underwent cataract surgery. After birth examination revealed that the infant was diagnosed with bilateral congenital cataracts at two days. Bilateral lens aspiration and anterior vitrectomy without intraocular lens insertion were done. Postnatal examinations and surgical interventions, including bilateral lens phacoemulsification and anterior vitrectomy without intraocular lens insertion, were conducted. This study discusses the importance of early detection, especially in familial cases, and the role of prenatal and postnatal care in managing congenital cataracts. It underscores the need for collaboration between ophthalmologists and obstetricians and the value of psychological support for the parents. The findings advocate for proactive fetal monitoring, particularly in genetically predisposed cases, to facilitate early diagnosis and treatment planning.

Clinical presentations of acquired comitant esotropia in 5-35 years old Japanese and digital device usage: a multicenter registry data analysis study.

PURPOSE: To describe clinical presentations of acquired comitant esotropia and digital device use in children, adolescents, and young adults without neurological problems. STUDY DESIGN: Multicenter prospective observational study. METHODS: Patients with acquired comitant esotropia, without intracranial diseases aged 5-35 years at the time of visit, who were seen at pre-registered facilities within 1 year of onset were enrolled. The duration from the onset of symptoms and the time of digital device usage approximately 1 month before onset and their lifestyles were surveyed. Visual acuity, cycloplegic refraction, and strabismus angles were measured. Data were analyzed in three age groups (Child: 5-12 years, Adolescent: 13-18 years, and Young adult: 19-35 years). RESULTS: Between November 2019 and December 2021, 218 patients were enrolled from 55 facilities, and 194 patients (including 62 children, 69 adolescents, and 63 young adults) were analyzed. The child group spent the least amount of time using digital devices (children: 159; adolescents: 210; young adults: 267 min/work day, p < 0.05; (mean time in the same order below) 229, 338, 314 min/holiday, p < 0.05) and had the largest strabismus angle (mean strabismus angle at near: 30, 22, 18 PD, p < 0.01; at far: 28, 26, 21 PD, p<0.05). CONCLUSION: The clinical features of acquired comitant esotropia and hand-held digital device usage differed between children aged ≤ 12 years and older patients. This report gives the current clinical characteristics of young patients with acquired esotropia and digital device usage.

Identification of the Genes Coding for Carthamin Synthase, Peroxidase Homologs that Catalyze the Final Enzymatic Step of Red Pigmentation in Safflower (Carthamus tinctorius L.).

Carthamin, a dimeric quinochalcone that is sparingly soluble in water, is obtained from the yellow-orange corolla of fully blooming safflower (Carthamus tinctorius L.) florets. Carthamin is a natural red colorant, which has been used worldwide for more than 4500 years and is the major component of Japanese 'beni' used for dyeing textiles, in cosmetics and as a food colorant. The biosynthetic pathway of carthamin has long remained uncertain. Previously, carthamin was proposed to be derived from precarthamin (PC), a water-soluble quinochalcone, via a single enzymatic process. In this study, we identified the genes coding for the enzyme responsible for the formation of carthamin from PC, termed 'carthamin synthase' (CarS), using enzyme purification and transcriptome analysis. The CarS proteins were purified from the cream-colored corolla of safflower and identified as peroxidase homologs (CtPOD1, CtPOD2 and CtPOD3). The purified enzyme catalyzed the oxidative decarboxylation of PC to produce carthamin using O2, instead of H2O2, as an electron acceptor. In addition, CarS catalyzed the decomposition of carthamin. However, this enzymatic decomposition of carthamin could be circumvented by adsorption of the pigment to cellulose. These CtPOD isozymes were not only expressed in the corolla of the carthamin-producing orange safflower cultivars but were also abundantly expressed in tissues and organs that did not produce carthamin and PC. One CtPOD isozyme, CtPOD2, was localized in the extracellular space. Based on the results obtained, a model for the stable red pigmentation of safflower florets during flower senescence and the traditional 'beni' manufacturing process is proposed.

Novel HPS6 mutations identified by whole-exome sequencing in two Japanese sisters with suspected ocular albinism.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism, platelet dysfunction and ceroid deposition. We report suspected ocular albinism in two Japanese sisters, caused by mutations in the HPS6 (Hermansky-Pudlak syndrome 6) gene. Trio-based whole-exome sequencing (WES) identified novel compound heterozygous mutations in HPS6 (c.1898delC: mother origin and c.2038C>T: father origin) in the two sisters. To date, 10 associated mutations have been detected in HPS6. Although we detected no general manifestations, including platelet dysfunction, in the sisters, even in long-term follow-up, we established a diagnosis of HPS type 6 based on the HPS6 mutations and absence of dense bodies in the platelets, indicating that WES can identify cases of HPS type 6. To the best of our knowledge, this is the first report of HPS6 mutations in Japanese patients.

Characteristics and surgical outcomes of consecutive exotropia of different etiologies.

PURPOSE: To investigate the surgical results for consecutive exotropia with or without insertion abnormalities on the basis of the position of the lateral rectus muscle at surgery. METHODS: Patients with consecutive exotropia who had undergone medial rectus recession as a primary procedure or advancement of previously recessed medial rectus muscles from 2002 to 2012 were included in the study. The characteristics, postoperative courses, and final results were compared among 3 patient groups. The patients' characteristics including sex, refractive error, and age at the initial surgery were compared. The main outcome measures were the angles of deviation in the primary position and the average divergent drift per month after the exotropia surgery. RESULTS: Twenty-four eyes of 23 patients were investigated. The patients were divided into 3 groups according to insertion status: with normal muscle insertion (4 men, 4 women), slipped muscles (9 women), and stretched scars (2 men, 4 women). The preoperative angles of deviation at near differed significantly between the slipped muscle group and the normal muscle insertion group (P = 0.02). Only patients with normal insertions had significantly greater hyperopia in the nondominant eye (0.95 D) than in the dominant eye (0.53 D). The postoperative divergent shift per month was similar among the groups (0.3, 0.1, and 0.2 prism diopters per month in the slipped muscle, stretched scar, and normal muscle insertion groups, respectively; P = 0.70). CONCLUSIONS: Hyperopic anisometropia is an important factor in the natural course of outward drift. The postoperative course of advancement of the medial rectus muscle was equally stable in all 3 patient groups.

The identification of a vacuolar iron transporter involved in the blue coloration of cornflower petals.

The blue petal color of the cornflower (Centaurea cyanus) is caused by protocyanin, a kind of metalloanthocyanin, which is a self-assembled supramolecular metal complex pigment. Protocyanin is composed of six molecules of anthocyanin, six molecules of flavone, one ferric ion, and one magnesium ion. The ferric ion is essential for blue color development. Here, we identify the vacuolar iron transporter gene (CcVIT) from the blue petals of C. cyanus and its function is identified and characterized. The CcVIT transcript was observed only in the petals. Its amino acid sequence is highly homologous to the Arabidopsis thaliana (AtVIT1) and Tulipa gesneriana (TgVit1) vacuolar iron transporters. Heterologous expression of the CcVIT gene in yeast indicated that the corresponding gene product transports ferrous ion into vacuoles. Analysis of purple mutant-line petals clarified that the anthocyanin and flavone components were the same as those found in plants with blue petals, but the amount of iron ions in the colored cells decreased, and consequently the amount of blue protocyanin was reduced. The CcVIT gene was expressed even in purple mutant petals, however, an amino acid substitution (A236E) occurred in that case. This change in the CcVIT gene sequence also resulted in loss of iron transport activity. The CcVIT protein thus plays a critical role in the blue coloration of cornflower petals.

Plasma membrane-localized Al-transporter from blue hydrangea sepals is a member of the anion permease family.

In hydrangea sepals, an aluminum complex of delphinidin-3-O-glucoside is responsible for the development of the blue color, and co-existing copigments mediate the solubilization and stabilization of the blue Al-anthocyanin complex which is localized in the sepal vacuole. In addition, hydrangeas are Al-hyperaccumulators and exhibit tolerance to acidic soils, in which the toxicity is due to soluble Al ion. Therefore, an Al-absorbing transport and storage system must exist in hydrangea. Recently, we cloned vacuolar and plasma membrane-localized Al-transporters, HmVALT, and HmPALT1, which are both members of the aquaporin family. However, HmPALT1 was only expressed in the sepals, indicating that a different Al-transporter should exist for absorption and long-distance transportation in the hydrangea plant. Using genetic information and microarray analysis, we identified an additional aluminum transporter gene, HmPALT2, which belongs to a member of the anion permease. The transcript was expressed in all tissues of hydrangea plants, and a transient expression study indicated that the gene product is localized to the plasma membrane. The results of an aluminum tolerance assay using yeast cells showed that the HmPALT2 is also involved in the transport of other metal(loid)s. The over-expression of HmPALT2 in Arabidopsis resulted in aluminum-hypersensitivity, suggesting that HmPALT2 should work as an aluminum transporter into cells in planta.

Gene cloning and characterization of two NADH-dependent 3-quinuclidinone reductases from Microbacterium luteolum JCM 9174.

We used the resting-cell reaction to screen approximately 200 microorganisms for biocatalysts which reduce 3-quinuclidinone to optically pure (R)-(-)-3-quinuclidinol. Microbacterium luteolum JCM 9174 was selected as the most suitable organism. The genes encoding the protein products that reduced 3-quinuclidinone were isolated from M. luteolum JCM 9174. The bacC gene, which consists of 768 nucleotides corresponding to 255 amino acid residues and is a constituent of the bacilysin synthetic gene cluster, was amplified by PCR based on homology to known genes. The qnr gene consisted of 759 nucleotides corresponding to 252 amino acid residues. Both enzymes belong to the short-chain alcohol dehydrogenase/reductase (SDR) family. The genes were expressed in Escherichia coli as proteins which were His tagged at the N terminus, and the recombinant enzymes were purified and characterized. Both enzymes showed narrow substrate specificity and high stereoselectivity for the reduction of 3-quinuclidinone to (R)-(-)-3-quinuclidinol.

Tonoplast- and plasma membrane-localized aquaporin-family transporters in blue hydrangea sepals of aluminum hyperaccumulating plant.

Hydrangea (Hydrangea macrophylla) is tolerant of acidic soils in which toxicity generally arises from the presence of the soluble aluminum (Al) ion. When hydrangea is cultivated in acidic soil, its resulting blue sepal color is caused by the Al complex formation of anthocyanin. The concentration of vacuolar Al in blue sepal cells can reach levels in excess of approximately 15 mM, suggesting the existence of an Al-transport and/or storage system. However, until now, no Al transporter has been identified in Al hyperaccumulating plants, animals or microorganisms. To identify the transporter being responsible for Al hyperaccumulation, we prepared a cDNA library from blue sepals according to the sepal maturation stage, and then selected candidate genes using a microarray analysis and an in silico study. Here, we identified the vacuolar and plasma membrane-localized Al transporters genes vacuolar Al transporter (VALT) and plasma membrane Al transporter 1 (PALT1), respectively, which are both members of the aquaporin family. The localization of each protein was confirmed by the transient co-expression of the genes. Reverse transcription-PCR and immunoblotting results indicated that VALT and PALT1 are highly expressed in sepal tissue. The overexpression of VALT and PALT1 in Arabidopsis thaliana conferred Al-tolerance and Al-sensitivity, respectively.

A case of osteogenesis imperfecta type II caused by a novel COL1A2 gene mutation: endoscopic third ventriculostomy to prevent hydrocephalus.

Osteogenesis imperfecta (OI) is a hereditary connective tissue disorder caused by defects in type I collagen synthesis. OI is generally classified into four types (I to IV), and the clinical prognosis varies from a lethal outcome for type II and varying deformities for type III to a normal lifespan for the other types. We describe a female patient with biochemically confirmed OI caused by a novel mutation in the COL1A2 gene. Persistence of blue sclerae supported the diagnosis of OI type II. The case was complicated with obstructive hydrocephalus, for which endoscopic third ventriculostomy (ETV) was performed. The ETV was transiently effective for the obstructive hydrocephalus. The patient subsequently developed brain atrophy, partly through ischemic events after the ETV, which appeared to contribute to maintenance of smooth circulation of the cerebrospinal fluid. We conclude that continuous and adequate medical care including ETV can facilitate long-term survival even in lethal OI type II.

Magnetic resonance imaging of the medial rectus muscle of patients with consecutive exotropia after medial rectus muscle recession.

PURPOSE: To investigate the morphologic characteristics of the medial rectus muscle in patients with consecutive exotropia. DESIGN: Retrospective, nonrandomized, interventional study. PARTICIPANTS AND CONTROLS: Eleven eyes of 10 patients with consecutive exotropia were studied. Thirteen eyes of 13 age-matched normal subjects were studied as controls. METHODS: All of the patients underwent an advancement of a previously operated medial rectus muscle. Patients were divided into 3 groups based on the insertion of the medial rectus muscle: Normally recessed stretched scar, and slipped muscle. MAIN OUTCOME MEASURES: A comparison was made of the clinical findings, intraoperative findings, and distance from the limbus to the medial rectus muscle measured on magnetic resonance images among the groups. RESULTS: The medial rectus of 4 eyes of 3 patients had normally recessed insertions and 7 eyes had abnormal insertions (3 stretched scars, 4 slipped muscles). The clinical findings were not different among the 3 groups. The magnetic resonance images showed that the medial rectus muscle was located closest to the limbus in the control subjects and most distant in the patients with a slipped muscle (P<0.005). The clinical findings in the patients with a stretched scar and with normally recessed were indistinguishable. CONCLUSIONS: Magnetic resonance images of the medial rectus muscles of the control subjects and operated groups are significantly different morphologically. A slipped medial rectus muscle has characteristic magnetic resonance findings that are distinguishable from the muscle with normally recessed and stretched scar.

Severe Peters Plus syndrome-like phenotype with anterior eye staphyloma and hypoplastic left heart syndrome: proposal of a new syndrome.

Peters Plus syndrome is a very rare autosomal recessive condition characterized by ocular defects (typically Peters anomaly) and other systemic major/minor anomalies. Mutations in the B3GALTL gene encoding beta 1,3-glucosyltransferase have been found in virtually all patients with typical Peters Plus syndrome. We report on a female patient with unusually severe manifestations of Peters Plus syndrome, including anterior eye staphyloma, cleft lip and palate, and hypoplastic left heart syndrome (HLHS). Analysis of the B3GALTL gene revealed no mutation in the patient. To our knowledge, HLHS has not previously been reported in Peters Plus syndrome so far, and anterior staphyloma, a most severe defect of the anterior eye chamber, is also apparently rare in the syndrome. Our patient might represent a new syndrome of severe Peters Plus syndrome-like phenotype with anterior eye staphyloma and HLHS.

Involvement of S-adenosylmethionine-dependent halide/thiol methyltransferase (HTMT) in methyl halide emissions from agricultural plants: isolation and characterization of an HTMT-coding gene from Raphanus sativus (daikon radish).

BACKGROUND: Biogenic emissions of methyl halides (CH3Cl, CH3Br and CH3I) are the major source of these compounds in the atmosphere; however, there are few reports about the halide profiles and strengths of these emissions. Halide ion methyltransferase (HMT) and halide/thiol methyltransferase (HTMT) enzymes concerning these emissions have been purified and characterized from several organisms including marine algae, fungi, and higher plants; however, the correlation between emission profiles of methyl halides and the enzymatic properties of HMT/HTMT, and their role in vivo remains unclear. RESULTS: Thirty-five higher plant species were screened, and high CH3I emissions and HMT/HTMT activities were found in higher plants belonging to the Poaceae family, including wheat (Triticum aestivum L.) and paddy rice (Oryza sativa L.), as well as the Brassicaceae family, including daikon radish (Raphanus sativus). The in vivo emission of CH3I clearly correlated with HMT/HTMT activity. The emission of CH3I from the sprouting leaves of R. sativus, T. aestivum and O. sativa grown hydroponically increased with increasing concentrations of supplied iodide. A gene encoding an S-adenosylmethionine halide/thiol methyltransferase (HTMT) was cloned from R. sativus and expressed in Escherichia coli as a soluble protein. The recombinant R. sativus HTMT (RsHTMT) was revealed to possess high specificity for iodide (I-), bisulfide ([SH]-), and thiocyanate ([SCN]-) ions. CONCLUSION: The present findings suggest that HMT/HTMT activity is present in several families of higher plants including Poaceae and Brassicaceae, and is involved in the formation of methyl halides. Moreover, it was found that the emission of methyl iodide from plants was affected by the iodide concentration in the cultures. The recombinant RsHTMT demonstrated enzymatic properties similar to those of Brassica oleracea HTMT, especially in terms of its high specificity for iodide, bisulfide, and thiocyanate ions. A survey of biogenic emissions of methyl halides strongly suggests that the HTM/HTMT reaction is the key to understanding the biogenesis of methyl halides and methylated sulfur compounds in nature.

Novel iron-storage particles may play a role in aluminum tolerance of Cyanidium caldarium.

Cyanidium caldarium (Tilden) Geitler, a unicellular red alga, has extraordinarily high aluminum (Al) tolerance. Algal cells cultured in the presence or absence of Al were subjected to transmission electron microscopy and energy dispersive X-ray analysis. Substantial changes to the thylakoid lumens were observed for the algal cells cultured in medium containing 200 mM Al, while other organelles were largely unaffected. Several spherical electron-dense bodies were found in the cytoplasm near the nucleus of both of the control and Al-treated cells. Although high levels of Fe and P were found in the bodies of control cells, immunocytochemical and morphological analysis data did not match the criteria established for Fe-accumulating substances like ferritin and phytate. In addition to these elements, Al was found in the bodies of the Al-treated cells. These results suggest that the electron-dense bodies function as an Fe-storage site under normal culture conditions, and that sequestration of Al in these bodies contributes to the high Al tolerance exhibited by C. caldarium.

cDNA microarray analysis of gene expression during Fe-deficiency stress in barley suggests that polar transport of vesicles is implicated in phytosiderophore secretion in Fe-deficient barley roots.

To acquire Fe from soil, graminaceous plants secrete mugineic acid family phytosiderophores (MAs) from their roots. The secretion of MAs increases in response to Fe deficiency, and shows a distinct diurnal rhythm. We used a microarray that included 8987 cDNAs of rice EST clones to examine gene expression profiles in barley roots during Fe-deficiency stress. Approximately 200 clones were identified as Fe-deficiency-inducible genes, of which seven had been identified previously. In order to meet the increased demand for methionine to produce MAs, Fe-deficiency enhances the expression of genes that participate in methionine synthesis, as well as recycling methionine through the Yang cycle. Of these 200 genes, approximately 50 exhibited different transcription levels in Fe-deficient roots at noon and at night. Northern blot analysis of time course experiments confirmed that five of these genes exhibited a diurnal change in their level of expression. The diurnal changes in the expression of these genes suggest that polar vesicle transport is involved in the diurnal secretion of MAs.