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Normal tension glaucoma (NTG) is a complex optic neuropathy characterized by progressive retinal ganglion cell death and glaucomatous visual field loss, despite normal intraocular pressure (IOP). This condition poses a unique clinical challenge due to the absence of elevated IOP, a major risk factor in typical glaucoma. Recent research indicates that up to 21% of NTG patients have a family history of glaucoma, suggesting a genetic predisposition. In this comprehensive review using PubMed studies from January 1990 to December 2023, our focus delves into the genetic basis of autosomal dominant NTG, the only known form of inheritance for glaucoma. Specifically exploring optineurin (OPTN), TANK binding kinase 1 (TBK1), methyltransferase-like 23 (METTL23), and myocilin (MYOC) mutations, we summarize their clinical manifestations, mutant protein behaviors, relevant animal models, and potential therapeutic pathways. This exploration aims to illuminate the intricate pathogenesis of NTG, unraveling the contribution of these genetic components to its complex development. [ABSTRACT FROM AUTHOR]

Background/Aims To investigate the utility of a data-driven deep learning approach in patients with inherited retinal disorder (IRD) and to predict the causative genes based on fundus photography and fundus autofluorescence (FAF) imaging. Methods Clinical and genetic data from 1302 subjects from 729 genetically confirmed families with IRD registered with the Japan Eye Genetics Consortium were reviewed. Three categories of genetic diagnosis were selected, based on the high prevalence of their causative genes: Stargardt disease (ABCA4), retinitis pigmentosa (EYS) and occult macular dystrophy (RP1L1). Fundus photographs and FAF images were cropped in a standardised manner with a macro algorithm. Images for training/testing were selected using a randomised, fourfold cross-validation method. The application program interface was established to reach the learning accuracy of concordance (target: >80%) between the genetic diagnosis and the machine diagnosis (ABCA4, EYS, RP1L1 and normal). Results A total of 417 images from 156 Japanese subjects were examined, including 115 genetically confirmed patients caused by the three prevalent causative genes and 41 normal subjects. The mean overall test accuracy for fundus photographs and FAF images was 88.2% and 81.3%, respectively. The mean overall sensitivity/specificity values for fundus photographs and FAF images were 88.3%/97.4% and 81.8%/95.5%, respectively. Conclusion A novel application of deep neural networks in the prediction of the causative IRD genes from fundus photographs and FAF, with a high prediction accuracy of over 80%, was highlighted. These achievements will extensively promote the quality of medical care by facilitating early diagnosis, especially by non-specialists, access to care, reducing the cost of referrals, and preventing unnecessary clinical and genetic testing. [ABSTRACT FROM AUTHOR]

Background: The nuclear magnetic resonance (NMR) spectroscopic data for biological macromolecules archived at the BioMagResBank (BMRB) provide a rich resource of biophysical information at atomic resolution. The NMR data archived in NMR-STAR ASCII format have been implemented in a relational database. However, it is still fairly difficult for users to retrieve data from the NMR-STAR files or the relational database in association with data from other biological databases. Findings: To enhance the interoperability of the BMRB database, we present a full conversion of BMRB entries to two standard structured data formats, XML and RDF, as common open representations of the NMR-STAR data. Moreover, a SPARQL endpoint has been deployed. The described case study demonstrates that a simple query of the SPARQL endpoints of the BMRB, UniProt, and Online Mendelian Inheritance in Man (OMIM), can be used in NMR and structure-based analysis of proteins combined with information of single nucleotide polymorphisms (SNPs) and their phenotypes. Conclusions: We have developed BMRB/XML and BMRB/RDF and demonstrate their use in performing a federated SPARQL query linking the BMRB to other databases through standard semantic web technologies. This will facilitate data exchange across diverse information resources. [ABSTRACT FROM AUTHOR]

Purpose To describe the clinical and genetic features of Japanese patients with Best's vitelliform macular dystrophy (BVMD). Patients and methods This study examined 22 patients, including 16 probands from 16 families with BVMD. Comprehensive ophthalmic examinations were performed, including dilated funduscopy, full-field electroretinography (ERG) and electro-oculography (EOG). BEST1 mutation analysis was performed by Sanger sequencing. Results All 16 probands exhibited characteristic BVMD fundus appearances, abnormal EOG, and normal ERG responses with the exception of one diabetic retinopathy proband. Genetic analysis identified 12 BEST1 variants in 13 probands (81%). Of these, 10 variants (p.T2A, p. R25W, p.F80L, p.V81M, p.A195V, p.R218H, p.G222E, p.V242M, p.D304del and p.E306D) have been previously reported in BVMD, while two variants (p.S7N and p.P346H) were novel, putative disease-causing variants. Single BEST1 variants were found in 12 probands. The one proband with compound heterozygous variants (p.S7N and p.R218H) exhibited typical BVMD phenotypes (pseudohypopyon stage and vitelliruptive stage in the right and left eyes, respectively). Conclusions Twelve different variants, two of which (p.S7N and p.P346H) were novel, were identified in the 13 Japanese families with BVMD. Compound heterozygous variants were found in one proband exhibiting a typical BVMD phenotype. Our results suggest that BEST1 variants do play a large role in Japanese patients with BVMD. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is a leading cause of vision loss and blindness in the elderly. The dry form is more common and accounts for about 85~90% of AMD patients in US, while Japanese AMD patients predominantly progress to wet-form or polypoidal choroidal vasculopathy (PCV). Recent studies have shown HTRA1, a serine protease gene, as major risk factor for wet form AMD (De Wan et al., Science 2006). Furthermore, we reported that the Japanese typical wet form AMD patients showed significant association with ARMS2/HTRA1 (Goto, Akahori et al., JOBDI 2009). The purpose of this study is to elucidate the function of ARMS2/HTRA1 gene promoter in wet-form AMD patients. The promoter sequence experiment showed that a great number of AMD patients had specific indel mutation in 3.8 kb upstream of HTRA1 gene. 2~3-fold increase of promoter activity was observed in indel HTRA1 promoter compared to control sequence (Iejima et al., JBC 2015). Furthermore, we created transgenic mice ubiquitously overexpressing mouse HtrA1 using the chicken act in promoter, continuous induction of HtrA1 in vivo was shown to lead to CNV, similar to wet AMD patients (Nakayama, Iejima et al., IOVS 2014). These results suggest that human HTRA1 expression is enhanced by AMD specific indel mutation in the promoter region of HTRA1 gene, and this enhanced HTRA1 may be concerned with induce retinal neovasucularization. [ABSTRACT FROM AUTHOR]

Purpose. To determine whether organic electroluminescence (OLED) screens can be used as visual stimulators to elicit patternreversal visual evoked potentials (p-VEPs). Method. Checkerboard patterns were generated on a conventional cathode-ray tube (S710, Compaq Computer Co., USA) screen and on an OLED (17 inches, 320 x 230 mm, PVM-1741, Sony, Tokyo, Japan) screen. The time course of the luminance changes of each monitor was measured with a photodiode. The p-VEPs elicited by these two screens were recorded from 15 eyes of 9 healthy volunteers (22.0 ± 0.8 years). Results. The OLED screen had a constant time delay from the onset of the trigger signal to the start of the luminescence change. The delay during the reversal phase from black to white for the pattern was 1.0msec on the cathode-ray tube (CRT) screen and 0.5msec on the OLED screen. No significant differences in the amplitudes of P100 and the implicit times of N75 and P100 were observed in the p-VEPs elicited by the CRT and the OLED screens. Conclusion. The OLED screen can be used as a visual stimulator to elicit p-VEPs; however the time delay and the specific properties in the luminance change must be taken into account. [ABSTRACT FROM AUTHOR]

Purpose. To investigate genetic and clinical features of patients with rhodopsin (RHO) mutations in two Japanese families with autosomal dominant retinitis pigmentosa (adRP). Methods. Whole-exome sequence analysis was performed in ten adRP families. Identified RHO mutations for the cosegregation analysis were confirmed by Sanger sequencing. Ophthalmic examinations were performed to evaluate the RP phenotypes. The impact of the RHO mutation on the rhodopsin conformation was examined by molecular modeling analysis. Results. In two adRP families, we identified two RHO mutations (c.377G>T (p.W126L) and c.1036G>C (p.A346P)), one of which was novel. Complete cosegregation was confirmed for each mutation exhibiting the RP phenotype in both families. Molecular modeling predicted that the novel mutation (p.W126L) might impair rhodopsin function by affecting its conformational transition in the light-adapted form. Clinical phenotypes showed that patients with p.W126L exhibited sector RP, whereas patients with p.A346P exhibited classic RP. Conclusions. Our findings demonstrated that the novel mutation (p.W126L) may be associated with the phenotype of sector RP. Identification of RHO mutations is a very useful tool for predicting disease severity and providing precise genetic counseling. [ABSTRACT FROM AUTHOR]

Background: We report our findings in two siblings with late-onset cone-rod dystrophy (CRD) with no visible macular degeneration. Cases and methods: Case 1 was an 82-year-old man who first noticed a decrease in vision and color blindness in his early seventies. His mother and younger sister also had visual disturbances. His decimal visual acuity was 0.3 in the right eye and 0.2 in the left eye. Ophthalmoscopy showed normal fundi, and fluorescein angiography was also normal in both eyes. The photopic single flash and flicker eletroretinograms (ERGs) were severely attenuated and the scotopic ERGs were slightly reduced in both eyes. Case 2 was the 80-year-old younger sister of Case 1. She first noticed a decline in vision and photophobia in both eyes in her early seventies. Her decimal visual acuity was 0.4 in the right eye and 0.2 in the left eye. Ophthalmoscopy showed mottling of the retinal pigment epithelium in the midperiphery with no visible macular degeneration. The photopic single flash and flicker ERGs were severely attenuated, and the scotopic ERGs were slightly reduced in both eyes. Conclusion: These siblings are the oldest reported cases of CRD with no visible macular degeneration. Thus, CRD should be considered in patients with reduced visual acuity, color blindness, and photophobia even if they are older than 70 years. [ABSTRACT FROM AUTHOR]

Objective: To characterize the phenotype of a white patient with occult macular dystrophy (OMD) and her clinically unaffected family members and to determine whether similar mutations were present in the RP1L1 gene in this family. Occult macular dystrophy is a rare macular dystrophy with central cone dysfunction hidden behind a normal fundus appearance that has been attributed to a mutation in the retinitis pigmentosa 1-like 1 (RP1L1) gene in 4 Japanese families. Methods: In this observational cross-sectional study of 1 white family with OMD, patients meeting the clinical criteria for OMD and their family members were evaluated by use of multifocal electroretinography, the Farnsworth D-15 color vision test, automated perimetry, spectral- domain optical coherence tomography (SD-OCT), fundus autofluorescence, and fundus photography. Fluorescein angiography was performed only on the proband. Members of this family were screened for genetic mutations in the RP1L1 gene. Results: In the family studied, the clinically affected proband was noted to have loss of the foveal outer segments and absence of bowing of the inner segment/ outer segment junction on SD-OCT scans. In addition, 1 clinically unaffected family member also demonstrated loss of the foveal photoreceptor outer segments and, therefore, decreased bowing of the inner segment/outer segment junction on SD-OCT scans. The fundus autofluorescence images of the eyes of the proband and her family members were normal. Although mutations in the RP1L1 gene have been identified in sporadic and autosomal dominant OMD pedigrees, no mutations in the RP1L1 gene were found in any of the participants. Conclusions: Loss of the outer segments of foveal photoreceptors can be detected and quantified by use of SDOCT in patients with OMD. Similar findings are present in some clinically unaffected family members and may represent subclinical manifestations of the disease. Although mutations in the RP1L1 gene have been described in several Japanese families with OMD, there were no such mutations in this white family of European descent, which suggests that inherited OMD is a genetically heterogeneous disorder. [ABSTRACT FROM AUTHOR]

Retinitis pigmentosa (RP) is the most common inherited human eye disease resulting in night blindness and visual defects. It is well known that the disease is caused by rod photoreceptor degeneration; however, it remains incurable, due to the unavailability of disease-specific human photoreceptor cells for use in mechanistic studies and drug screening. We obtained fibroblast cells from five RP patients with distinct mutations in the RP1, RP9, PRPH2 or RHO gene, and generated patientspecific induced pluripotent stem (iPS) cells by ectopic expression of four key reprogramming factors. We differentiated the iPS cells into rod photoreceptor cells, which had been lost in the patients, and found that they exhibited suitable immunocytochemical features and electrophysiological properties. Interestingly, the number of the patient-derived rod cells with distinct mutations decreased in vitro; cells derived from patients with a specific mutation expressed markers for oxidation or endoplasmic reticulum stress, and exhibited different responses to vitamin E than had been observed in clinical trials. Overall, patient-derived rod cells recapitulated the disease phenotype and expressed markers of cellular stresses. Our results demonstrate that the use of patient-derived iPS cells will help to elucidate the pathogenic mechanisms caused by genetic mutations in RP. [ABSTRACT FROM AUTHOR]

A series of phosphorescent cyclometalated iridium(iii) complexes 4–6 with new ligands of bicyclic phenylvinylpyridines have been synthesized and systematically examined for their photophysical, electrochemical and electroluminescence (EL) properties. All of the bis- and tris-cyclometalated complexes could be characterized by 1H-NMR, elemental analysis and X-ray crystal structure analysis. The phosphorescence colour of the complexes in solution, the solid state and polymer film is unusually changed depending on the structure of the ligand. EL devices using the complexes exhibited external quantum efficiencies (EQE) of 1.2–8.1% at 100 cd m−2, and EL colour tuning in the range of 571–635 nm was achieved analogous to PL properties of the phosphors. X-Ray analyses of complexes 4a–c demonstrated that the degree of steric hindrance increases with an increase of the cycloalkane ring size, leading to hypsochromic shifts of emission by the distortion of the phenyl groups. X-Ray analyses also suggested that long iridium–carbon bonds are unfavorable for efficient electroluminescence. In addition, we have found a unique and important aspect for the study of EL devices: the EL devices based on complexes 4c, 6a show moderate EL efficiencies (EQE = 4.0 and 6.1%) although these complexes have no emission in solution at room temperature, indicating that the PL properties of the complexes in solution are not directly related to the EL efficiencies. [ABSTRACT FROM AUTHOR]

The author reflects on the development of Asian Eye Genetics Consortium's (AEGC) Indian Chapter. Topics discussed include an overview of AEGC, the developments of AEGC, the 73rd Annual Conference of All India Ophthalmological Congress in New Delhi, India, the emphasis of AEGC on genotype and phenotype information collection, and the previous meetings of AEGC.