IMPG2 gene variations can cause inherited retinal dystrophy (IRD).The clinical phenotypes of IMPG2 related IRD are heterogeneous, including retinitis pigmentosa, vitelliform macular dystrophy and occasionally Stargardt-like macular dystrophy.There is a certain correlation between the variation type and the clinical phenotype.The compound heterozygous/homozygous IMPG2 variations predominantly cause autosomal recessive retinitis pigmentosa, while heterozygous mutations is typically associated with autosomal dominant vitelliform macular dystrophy showing incomplete dominance.IMPG2 expressed by retinal photoreceptors encodes interphotoreceptor matrix, though its pathogenesis remains unclear.Studies suggest variations may cause mislocalization of matrix components, aberrant energy metabolism and impaired autophagy in the retina.This review summarizes IMPG2-related IRD phenotypes and advances in pathogenic mechanisms, providing theoretical support for clinical diagnosis, therapy and research.

Objective:To explore the effect of exercise on the memory of rats modeling vascular cognitive impairment (VCI) and also its effects on the hippocampal Sema3G/neuropilin-2 (Nrp2)/PlexinA4 signaling pathway.Methods:Eighteen male Sprague-Dawley rats were randomly divided into a sham-operated group, a model group, and an exercise group, each of 6. The model and exercise groups underwent VCI modeling via bilateral common carotid artery occlusion, while the sham-operated group received the same surgical procedure without vessel ligation or transection. Beginning forty-eight hours after the surgery, the exercise group carried out daily 30-minute treadmill training sessions, 5 days a week, for a total of 4 weeks, while the other two groups were placed on the same treadmill with it not in operation. After the intervention, cognitive functioning was assessed using the novel object recognition (NOR) test and a Y-maze test. Western blotting was employed to evaluate the expression of Sema3G, Nrp2, PlexinA4, and Rac1 in the hippocampus. Immunofluorescence staining was used to observe the distribution of Nrp2 and PlexinA4 in the hippocampus.Results:Compared with the model group, the exercise group exhibited significantly higher NOR indices during both the short-term and long-term memory testing phases after the intervention. Those rats also tended to have significantly longer total exploration times in the novel arm of the Y-maze test. The western blotting revealed that the expression levels of Sema3G, PlexinA4, and Rac1 in the hippocampus were significantly higher in the exercise group compared to the model group, on average. Immunofluorescence showed significantly increased PlexinA4 fluorescence intensity in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus, and significantly elevated Nrp2 fluorescence intensity in the CA3 region in the exercise group compared to the model group. The Pearson correlation coefficients for Nrp2/PlexinA4 co-localization in the CA1, CA3 and DG regions were significantly higher in the exercise group than in the model group.Conclusions:Exercise training significantly improves memory function in rats with VCI, and this effect may be associated with activation of the hippocampal Sema3G/Nrp2/PlexinA4 signaling pathway.

Objective:To explore the effect of exercise on the memory of rats modeling vascular cognitive impairment (VCI) and also its effects on the hippocampal Sema3G/neuropilin-2 (Nrp2)/PlexinA4 signaling pathway.Methods:Eighteen male Sprague-Dawley rats were randomly divided into a sham-operated group, a model group, and an exercise group, each of 6. The model and exercise groups underwent VCI modeling via bilateral common carotid artery occlusion, while the sham-operated group received the same surgical procedure without vessel ligation or transection. Beginning forty-eight hours after the surgery, the exercise group carried out daily 30-minute treadmill training sessions, 5 days a week, for a total of 4 weeks, while the other two groups were placed on the same treadmill with it not in operation. After the intervention, cognitive functioning was assessed using the novel object recognition (NOR) test and a Y-maze test. Western blotting was employed to evaluate the expression of Sema3G, Nrp2, PlexinA4, and Rac1 in the hippocampus. Immunofluorescence staining was used to observe the distribution of Nrp2 and PlexinA4 in the hippocampus.Results:Compared with the model group, the exercise group exhibited significantly higher NOR indices during both the short-term and long-term memory testing phases after the intervention. Those rats also tended to have significantly longer total exploration times in the novel arm of the Y-maze test. The western blotting revealed that the expression levels of Sema3G, PlexinA4, and Rac1 in the hippocampus were significantly higher in the exercise group compared to the model group, on average. Immunofluorescence showed significantly increased PlexinA4 fluorescence intensity in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus, and significantly elevated Nrp2 fluorescence intensity in the CA3 region in the exercise group compared to the model group. The Pearson correlation coefficients for Nrp2/PlexinA4 co-localization in the CA1, CA3 and DG regions were significantly higher in the exercise group than in the model group.Conclusions:Exercise training significantly improves memory function in rats with VCI, and this effect may be associated with activation of the hippocampal Sema3G/Nrp2/PlexinA4 signaling pathway.

IMPG2 gene variations can cause inherited retinal dystrophy (IRD).The clinical phenotypes of IMPG2 related IRD are heterogeneous, including retinitis pigmentosa, vitelliform macular dystrophy and occasionally Stargardt-like macular dystrophy.There is a certain correlation between the variation type and the clinical phenotype.The compound heterozygous/homozygous IMPG2 variations predominantly cause autosomal recessive retinitis pigmentosa, while heterozygous mutations is typically associated with autosomal dominant vitelliform macular dystrophy showing incomplete dominance.IMPG2 expressed by retinal photoreceptors encodes interphotoreceptor matrix, though its pathogenesis remains unclear.Studies suggest variations may cause mislocalization of matrix components, aberrant energy metabolism and impaired autophagy in the retina.This review summarizes IMPG2-related IRD phenotypes and advances in pathogenic mechanisms, providing theoretical support for clinical diagnosis, therapy and research.

Objective:To observe and analyze the rate of visual acuity progression and binocular symmetry in patients with choroideremia (CHM).Methods:A single-center retrospective longitudinal cohort study. From April 2009 to August 2022, 38 eyes of 19 patients diagnosed with CHM through clinical and genetic testing at the Department of Ophthalmology, Peking Union Medical College Hospital, were included in this study. All patients underwent at least 2 follow-up visits with a minimum interval of 1 year between visits, and binocular best-corrected visual acuity (BCVA) results were recorded at each follow-up visit. Decimal visual acuity was converted into logarithm of the minimum angle of resolution (logMAR) for analysis. The patient group consisted of 19 males from 16 unrelated families. The age at initial visit was (39.52±13.24) years, with a (2.63±1.61) follow-up visits over a duration of (4.95±2.68) years. A total of 50 binocular BCVA data were included. Annual progression rate of visual acuity was calculated based on longitudinal and cross-sectional data. Spearman correlation coefficient and Bland-Altman method were used to evaluate the binocular symmetry.Results:The rate of visual acuity progression was (0.095±0.148) logMAR units/year based on longitudinal data and (0.018±0.009) logMAR units/year based on cross-sectional data. The binocular symmetry for BCVA of the baseline values was strong; however, the binocular symmetry of progression rates for BCVA was moderate. Spearman correlation analysis showed that binocular symmetry in baseline BCVA was high ( r=0.881, P<0.001). The symmetry of binocular vision progression rates based on longitudinal data was moderately symmetric ( r=0.528, P=0.020). Bland-Altman analysis showed that 94.7% of binocular baseline BCVA differences were within 95% confidence interval ( CI) of 95% limit difference (LOA), indicating good symmetry of binocular baseline BCVA. The number of binocular BCVA progression rate differences within 95% CI of 95%LOA was 89.5%, suggesting moderate symmetry in binocular BCVA progression rate. The results of Spearman correlation coefficient and Bland-Altman analysis of binocular symmetry were basically consistent. Conclusions:The rate of visual acuity progression of patients with CHM based on longitudinal and cross-sectional data is (0.095±0.148) and (0.018±0.009) logMAR units/year, respectively. Cross-sectional data from patients of different ages should not be used to infer the progression rate of the natural history. Binocular eyes with highly symmetrical baseline visual acuity may differ in the rate of visual acuity progression.

Choroideremia (CHM) is a rare inherited eye disease that leads to blindness. It is caused by pathogenic variants in the CHM gene and exhibits X-linked recessive inheritance. Affected males present with progressively worsening night blindness, visual field loss, and decreased central vision, which can cause blindness in middle age. Although female carriers typically exhibit mild symptoms, it is essential to understand their clinical features for early diagnosis of patients as well as genetic counseling of family members. Currently, the recognition and diagnosis rates of CHM among ophthalmologists in various regions and levels of hospitals in China still need to be improved. A standardized clinical pathway is needed to meet the diagnostic and treatment needs of patients. Led by the the Chinese Hereditary Ocular Disease Diagnosis and the Treatment Group and the Chinese Hereditary Ocular Disease Alliance, based on existing evidence both domestically and internationally, the Expert consensus on diagnosis and treatment of choroideremia (2024) has been compiled, systematically and comprehensively elaborating on the standardized clinical pathways for CHM. Interpreting the key points of this consensus will help highlight its core points and ideas, enhancing the standardization and effectiveness of the diagnosis and treatment of CHM by ophthalmologists from all levels of hospitals.

Blau syndrome is a rare genetic disorder characterized by the a mix of granulomatous arthritis, uveitis, and dermatitis. Patients typically manifest multisystem involvement, including ocular, skin, and skeletal abnormalities. Blau syndrome is extremely rare, with a global incidence of less than one in a million among children. In this multidisciplinary consultation, we present a case of a 21-year-old young female patient having multisystemic involvement since early childhood. She was presented with multiple joint swelling, skin lesions, increased eye discharge, and accompanied by hypertension and arterial abnormalities, and received a diagnosis of uveitis. The patient had been receiving steroid treatment since the age of 6 and has tried various medications, with some improvement in joint swelling and ocular symptoms. Through this rare disease multidisciplinary consultation, we aim to provide guidance in the molecular diagnosis of the patient, multisystem assessment, and the selection and formulation of treatment plans. Additionally, we hope that by reporting this case, clinical physicians can gain a better understanding of the diagnosis and comprehensive treatment strategies for Blau syndrome, thereby improving the management and treatment of rare diseases.

Objective:To identify the clinical characteristics and pathogenic gene of a Chinese Han family with achromatopsia (ACHM).Methods:The method of pedigree investigation was adopted.A Chinese Han ACHM family was recruited in Peking Union Medical College Hospital form July 2010 to July 2019, including 5 members of 2 generations.There were 2 patients and 3 phenotypically normal individuals.The medical history was collected and comprehensive ophthalmic examinations were performed, including visual acuity, colour vision, color fundus photography, fundus autofluorescence (FAF), optical coherence tomography (OCT), visual field and electroretinogram (ERG).Genomic DNA was extracted from peripheral blood sample from the patients and family members.Pathogenic variant was screened by whole exome sequencing (WES) and verified by Sanger sequencing and co-segregation analysis.The variant was annotated with the 1000 Genomes, Human Gene Mutation Database (HGMD), ExAC, ClinVar and OMIM databases to detect the single nucleotide polymorphism and whether it had been reported previously.The pathogenicity of the variant was evaluated according to the standards and guidelines of the American College of Medical Genetics and Genomics (ACMG).This study adhered to the Declaration of Helsinki.The study protocol was approved by the Institutional Review Board of Peking Union Medical College Hospital (No.JS-2059).Written informed consent was obtained from the guardians of juvenile patients.Results:There was consanguinity between the proband's parents and this family was consistent with autosomal recessive inheritance.Both male patients presented the reduction of visual acuity accompanied with photophobia and color blindness since childhood.Barely visible foveal light reflex in fundus images, hypofluorescence of foveal areas in FAF images, foveal defect with disruption of ellipsoid zone and interdigitation zone in OCT images were found in both patients.Central scotoma with or without peripheral visual field defects was detected.Generally normal scotopic 0.01, 3.0 and 10.0 responses, decreased oscillatory potentials amplitudes, no photopic 3.0 and 30 Hz flicker responses were observed.No sign of progression was found during the 9-year follow-up.It was confirmed that both patients carried a novel homozygous disease-causing variant c. 947insA (p.Asn316Lysfs*46) in ATF6 gene.Their mother had the heterozygous variant.The unaffected brother did not carry the variant.This family was consistent with co-segregation.This variant was labeled as pathogenic according to the ACMG standards and guidelines. Conclusions:A novel variant c.947insA (p.Asn316Lysfs*46) in ATF6 gene is the pathogenic variant of this achromatopsia family.This is the first time that this variant has been reported.

Gene therapy is expected to restore the function of genetic material fundamentally and it has become a new trend in inherited retinal dystrophy treatment.Antisense oligonucleotide (AON) is a kind of small molecule nucleic acid drug, which can specifically bind to messenger RNA through the base pairing principle, thus interfering or modifying gene expression at the transcription and translation level.Possessing the advantages of high specificity and efficiency, wide targeting range, low immunogenicity and limited adverse effect, AON has become a novel remedy for inherited retinal dystrophy.Currently, three different AON drugs have already been used in clinical trials for inherited retinal dystrophy.In this review, the chemical structure modification, properties and mechanism of AON, and the therapeutic strategies of AON in different inherited retinal dystrophy diseases in recent years were summarized.

A 15-year-old female was referred to the hospital with intermittent fever, where multiple systemic abnormalities were found, such as splenomegaly, secondary hypersplenism, retinitis pigmentosa, and ectodermal dysplasia. Medical history revealed that she had suffered recurrent respiratory infections, blurred vision at night, and dysplasia of teeth and nail beds since childhood. Then she was suspected to be experiencing ROSAH syndrome, a rare disease newly recognized in recent years, which was finally confirmed by gene sequencing results. During a course of treatment with tumor necrosis factor inhibitors, recurrent fever with elevated inflammatory markers reappeared, and the child developed headaches. To guide the comprehensive treatment and improve the patient's quality of life, the multidisciplinary team in Peking Union Medical College Hospital discussed together and directed the following treatment.