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Axenfeld-Rieger syndrome is a rare autosomal dominant hereditary disease characterized by anterior segment dysgenesis, which may be accompanied by various systemic defects, including craniofacial dysmorphism, hypodontia, microdontia, and redundant periumbilical skin.Its typical ocular manifestations include posterior embryotoxon, iris hypoplasia, peripheral anterior synechiae, corectopia and polycoria with a high prevalence of glaucoma.Patients can exhibit any combination of these features.However, family members with the same genotype may present different phenotypes due to phenotypic heterogeneity.Emerging evidence suggests that PITX2 and FOXC1 genes encoding transcription factors are primarily associated with genetic variants in ARS.Intragenic mutations and gene deletions are common types of genetic variations suspected to trigger changes in gene dosages and protein function.However, the underlying molecular mechanism remains unclear.Some patients with ARS carry mutations in the COL4A1, PRDM5, and CYP1B1 genes, but the pathogenicity of these variations has yet to be confirmed by further studies.This article provided an overview of the typical clinical features, potential correlations between phenotype and genotype, as well as gene function.
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Visual behaviorally operant method is one of the main detections for identifying animal models of visual diseases, which is mainly through the optomotor response (OMR) and optokinetic reflex (OKR) stimulated by the virtual operating system (VOS). The automated VOS was commonly used as a powerful tool to control the contrast sensitivity and measure the spatial frequency of the monitoring device by adjusting parameters such as grating fringe width, rotation velocity and light intensity, and also to track the OKR, OMR, and the combined movement of OKR and OMR.Both the optimized measuring methods and evaluation indicators including the search coils, the corneal labeling, OMR-arena system, the OMR index, the staircase protocol tests and the improved stimuli from two-dimensional to three-dimensional helped to ensure the validity of test data.Moreover, the introduction of image recognition technology benefited in extracting the body and head contours of mice.Computer algorithms such as deep learning were also applied to analyze and process the visual behavior of diseased mice, which promoted sensitivity, shortened testing time, reduced detection errors and improved data accuracy.For all the factors mentioned, the VOS could be used as an effective research tool for glaucoma, cataract, retinopathy, hereditary eye disease, optic nerve degeneration and others.This article reviewed the value of VOS for visual behavioral assessment in mice models of visual disease from the visual detection methods and assessment indicators.
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Objective:To identify disease-causing variation in a Chinese family with Axenfeld-Rieger syndrome (ARS) through the analysis of clinical symptoms and hereditary information.Methods:The method of pedigree investigation was adopted.A Chinese ARS family including 15 family members of 3 generations was recruited in the Second Affiliated Hospital of Harbin Medical University in 2018.There were 3 patients in the family.The family history and clinical data were collected.Ophthalmic and general examinations were carried out in all the members included.DNA and RNA were extracted from collected peripheral venous blood samples of 2-5 ml from each member.Whole exome sequencing was used to screen the variations in the proband.Suspected variations screened through searching population databases and bioinformatics analysis were verified by Sanger sequencing and real-time quantitative PCR.Conservation analysis and deleteriousness prediction of suspected variations were conducted.The pathogenecity of candidate rare variations were evaluated according to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines.This study followed the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the Second Affiliated Hospital of Harbin Medical University (No.KY2019-231).Written informed consent was obtained from each subject or custodian prior to entering the study cohort.Results:The 3 patients all had typical ARS clinical features in eyes, teeth and umbilicus, and carried the same heterozygous variant, c.525delC (p.Asp175Glufs *) in the PITX2 gene, which were not found in other members, indicating co-segregation.The relative expression of PITX2 mRNA was 0.672±0.063 in the patients, which was significantly lower than 1.015±0.179 in the healthy controls ( t=8.847, P<0.001).This variant was not recorded in dbSNP, 1000G, gnomeAD, ExAC, Korea1K and EVS databases, and it was labelled as deleterious by MutationTaster.The affected conservative amino acid sequences were found in 9 species.The variant was determined as pathogenic according to the ACMG standards and guidelines. Conclusions:The c.525delC (p.Asp175Glufs *) mutation of PITX2 gene is pathogenic in the pedigree.This is the first time that this mutation has been reported in Chinese family with ARS.
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Glaucoma is a disorder that leads to retinal ganglion cells (RGCs) apoptosis, visual field loss and optic nerve degeneration.The RGCs death is irreversible, which limites their ability for axon regeneration after injury.Bone marrow mesenchymal stem cells (BMSCs) have shown promise as cell-incorporation, cell-supplements and paracrine-mediated therapy for compromised neurons, which have allowed the possibility of the pluripotent BMSCs based regeneration of retinal cells and repair of neurodegenerative diseases.Intravitreal injection, subretinal injection and autologous BMSCs homing transplantation were explored as therapy for various retinal injury conditions.These BMSCs primarily have paracrine trophic effects and can also incorporate into the damaged retina directly, which have regenerative and protective effects on the reduce of RGCs apoptosis and retinal nerve fiber loss, and multiple cell signals and mechanisms are involved.This review provides an update of the current evidence of BMSCs as treatment and potential limitations, and complications for glaucomatous RGCs dysfunction.The researches including induced-differentiation, transplantation methods and the potential neuroprotective mechanism of BMSCs as therapy for glaucomatous retinal degeneration were discussed.
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Objective To assess the prevalence and binocular dysfunctional risk factors associated with asthenopia among adult myopes.Methods The study population included 800 adult myopes,a cross-sectional visual parameters that characterize the accommodative:accommodation amplitude (AA),accommodative facility,and accommodative response (fused crossed cylinder-FCC) and binocular function (near and distant horizontal and vertical associated phorias,near and distance negative and positive fusional vergence,near point of convergence,negative and positive relative accommodation (NRA/PRA),stimulus AC/A ratio and stereoacuity) were evaluated when these subjects wore adequate spectacle correction.Results Asthenopia was reported in 24.2％ (194/800) of myopes.The incidence of asthenopia in female (27.8％,128/460) was more than that in male (19.4％,66/340),and there was significant difference (P =0.006).In univariate analysis,the monocular AA,binocular AA,NRA and PRA were significantly associated with asthenopia (P =0.000).In multivariate analysis,low NRA (≤1.25 D),low NRA (≤1.50 D) were significant risk factors for asthenopia (P =0.000,OR =7.644 ;95％ CI 2.913-17.580;P =0.000,OR =5.303;95％ CI 2.822-16.205).Conclusion Preventive measures directed against the binocular dysfunctional risks factors associated with asthenopia may help reduce the prevalence and provide a positive impact on asthenopia.