The treatment of hereditary retinopathy depends on gene replacement or editing therapy, and adeno-associated virus (AAV) vector is one of the most widely used gene transfer vectors. The delivery methods of AAV vector-mediated target genes to the retina inlucde intravitreal injection, subretinal injection, and suprachorioidal injection. Intravitreal injection of AAV vector is currently the most commonly used delivery route, which can effectively improve the functions of retina disorders such as blinding retinal dystrophy in mice. Subretinal injection of AAV vector can deliver the target gene to the local retina, resulting in stronger efficiency of transfection and gene expressio, however, the high technical operations are required. In recent years, as a new high-profile delivery route suprachorioidal injection of AAV vector can achieve more extensive transfection of target genes in the retina of rabbits and rats. At present, the efficiency of AAV vector transduction in the retina is affected by the delivery mode. In the future, it is necessary to further explore the effect of AAV vector delivery mode on the transduction efficiency in order to find an important delivery route for mediating gene therapy for retinal diseases.

Microglia are the resident macrophages in the central nervous system (CNS), like Kupffer cells in the liver and dust cells in the lung.Cell function is decided by cell properties (like structure determining function) and location.As retina is a part of nervous system, the eyes are an extension of brain.CNS consists of brain, spinal cord and retina.CNS plays a vital role in the body, thus the surrounding microglia based on the ordinary macrophages have many features.Microglia are the sentry of CNS, exerting immune surveillance, immune defense, neuron toxicity, promoting synapse formation and synaptic pruning.Being the most representative immune cells in CNS, microglia become the research focus of nervous system disease pathogenesis.The dual role of microglia in neuron protection and nerve toxicity is due to the different materials synthesized and secreted in response to a series of pathological changes.At present, the study of microglia in nervous system diseases especially retina disease has attracted more and more attention.In this review, the research progress and problems to be solved of microglia in retina disease and nervous system disease involving the retina were described, hoping to provide help in further research on microglia.

Myopia is a common refractive eye disease, which is an ametropia in which the spherical equivalent of the eye is less than or equal to -0.50 D, or the axial length of the eye is more than 24 mm.As myopia progresses, the likelihood of ocular complications gradually increases, including retinal detachment, retinal neovascularization, macular degeneration, and other pathological changes.In recent years, the annual incidence of myopia has increased significantly and has become the second leading cause of blindness worldwide.Epidemiologic studies have shown that the distribution of myopia presents obvious ethnic differences and familial clustering characteristics, indicating that genetic factors play an important role in the onset and development of myopia.In addition, researchers have identified many pathogenic variants and candidate genes for myopia in patient samples, revealing the genetic and molecular mechanisms of myopia development.The genetic factor not only can serve as the independent factor that affects myopia development but also can interact with the environmental factor and together control the progression of myopia.This article reviewed the epidemiological research evidence on the heritability of myopia, the genetic factors of myopia development, and the interaction between genetic and environmental factors to provide new ideas for the prevention, control and treatment of myopia.

Objective: To analyze the clinical symptoms and hereditary information of suspicious juvenile neuronal ceroid-lipofuscinosis (JNCL) and determine the genotype in order to explore the diagnosis clues in the patients with ophthalmologic manifestations being initial symptom. Methods: A case-control study was performed in this study.Two families were included in Eye Hospital of Wenzhou Medical in 2013 and 2017, respectively.Medical histories were collected and all participants underwent comprehensive ophthalmologic examinations, and the best corrected visual acuity (BCVA) was obtained.Fundus photography and optical coherence tomography (OCT) were used to image the retinal signs, and visual electrophysiology was recorded to evaluate the visual function.Genomic DNA of 3 patients who initially visited to ophthalmologists and 5 unaffected family members were extracted.Whole exome sequencing (WES), targeted exome sequencing (TES), Sanger sequencing and comprehensive analyses of pathogenicity were performed to determine the genetic cause of the patients.This study was approved by Ethics Committee of Eye Hospital of Wenzhou Medical University (KYK-2017-7), and written informed consent was obtained from each subject prior to any medical examination. Results: All patients presented bull eye sign and disorder of pigment on the fundus photograph, and the retinas were thinning on the OCT image, indicating the diffuse retinal pigment epithelium atrophy of macula and loss of outer layer structure of retina.Three mutations in CLN3 gene were identified by WES, TES, Sanger validation and assessments of pathogenicity, including c. 154T>C(p.Y52H), c.982G>C(p.A328P) and c. 906+ 5G>A, among which p. A328P was a novel mutation.Patients of F1 family harbored the compound heterozygous mutations c. 154T>C (p.Y52H) and c. 982G>C(p.A328P), while proband of F2 family harbored the homozygous splice site mutation c. 906+ 5G>A, which was reported to be a pathogenic mutation of JNCL.Co-segregation and comprehensive pathogenicity analysis revealed that the compound heterozygous mutations in F1 family and the homozygous mutation in a splice site in F2 family were the genetic causes of their phenotypes. Conclusions A novel mutation in CLN3 gene for JNCL is identified, which expands the mutation spectrum of CLN3 gene.Considering the high clinical heterogeneity of inherited retinal diseases, especially syndromic cases, genetic test through next generation plays a vital role in diagnosis, guiding future treatment and prognostic evaluation.

High myopia has become a global public health issue, posing a significant threat to visual health. There are still some problems in the process of diagnosis and treatment, including the definition of high myopia and pathological myopia, opportunities and challenges of artificial intelligence in the diagnosis and treatment system, domestic and international collaboration in the field of high myopia, the application of genetic screening in children with myopia and high myopia patients, and the exploration of new treatment methods for high myopia. Nowadays, myopia and high myopia show the characteristics of early onset age and sharp rise in prevalence, and gradually become the main cause of low vision and irreversible blindness in young and middle-aged people. Therefore, it is of great significance to accurately define high myopia and pathological myopia, combine artificial intelligence and other methods for screening and prevention, promote cooperation in different fields, strengthen gene screening for early-onset myopia and adopt new and effective ways to treat it.

Objective:To observe the interobserver agreement of classification of macular degeneration in severe pathological myopia (PM) by ophthalmologists with different clinical experience.Methods:A retrospective study. From January 2019 to December 2021, 171 eyes of 102 patients with severe PM macular degeneration who were examined at Eye Center of Beijing Tongren Hospital of Capital Medical University were included in the study. The clinical data such as age, gender, axial length, spherical equivalent power, fundus color photography, and optical coherence tomography (OCT) were collected in detail. Six independent ophthalmologists (A, B, C, D, E, F) classified each fundus photography based on META-PM and ATN classification of atrophy (A) system and interobserver agreement was assessed by Kappa statistics. According to the classification standard of traction (T) in the ATN classification, the OCT images were interpreted and classified, in which T0 was subdivided into retinal pigment epithelium (RPE) and choroidal thinning, choroidal neovascularization (CNV) with partial RPE and choroidal atrophy, RPE, and choroidal atrophy. Lamellar macular hole can't be classified by ATN system, which was defined as TX. Kappa ( κ) test was used to analyze the consistency of classification results between physicians A, B, C, D, E and F. κ value ≤0.4 indicates low consistency, 0.4 < κ value ≤ 0.6 indicates moderate consistency, and κ value >0.6 indicates strong consistency. Results:Among the 171 eyes of 102 cases, there were 20 males with 37 eyes (19.6%, 20/102), and 82 females with 134 eyes (80.4%, 82/102); age was 61.97±8.78 years; axial length was (30.87±1.93) mm; equivalent spherical power was (-16.56±7.00) D. Atrophy (A) classification results in META-PM classification and ATN classification, the consistency of physician A, B, C, D, E and physician F were 73.01%, 77.19%, 81.28%, 81.28%, 88.89%; κ value were 0.472, 0.538, 0.608, 0.610, 0.753, respectively. In the ATN classification, the T0, T1, T2, T3, T4, and T5 were in 109, 18, 11, 12, 9, and 8 eyes, respectively; TX was in 4 eyes.Conclusions:There are differences in the consistency of classification of severe PM macular lesions among physicians with different clinical experience, and the consistency will gradually improve with the accumulation of clinical experience.

Objective:To systematically evaluate the effect of pars plana vitrectomy (PPV) combined total peeling of internal limiting membrane (ILM) versus fovea-sparing peeling of ILM for myopic foveoschisis.Methods:A evidence-based medicine study. Chinese and English as search terms for myopic foveoschisis, vitrectomy, and peeling of internal limiting membrane were used to search literature in China National Knowledge Infrastructure, Wanfang database, VIP database, PubMed of National Library of Medicine, Medline, Embase, and Cochrane Library. The high myopic macular schisis was selected as the research object, the intervention method was PPV combined with complete ILM peeling and combined with foveal preservation ILM peeling surgery clinical control study between Jan 1, 2010, and Jun 31, 2021. Incomplete or irrelevant literature and review literature were excluded. The method of Newcastle-Ottawa Scale system was used to evaluate the included literature. The literature was meta-analyzed by RevMan5.3 software. The mean difference ( MD) and a confidence interval ( CI) of 95% were used to describe the effect sizes of continuous data, fixed effects model was performed. The data including the best corrected visual acuity (BCVA), central fovea thickness (CFT), and postoperative macular hole (MH) were analyzed. Results:In those databases, 232 articles based search stratery were totally retrieved, and 10 articles (417 eyes) were finally included for meta-analysis with 245 eyes for PPV combined total peeling of ILM and 172 eyes for PPV combined fovea-sparing peeling of ILM. Meta-analysis results showed there was no significant difference in BCVA and CFT between the two groups (BCVA: MD=0.05, 95% CI 0.00-0.11; P>0.05; CFT: MD=-4.79, 95% CI -18.69-9.11, P>0.05). It was compared with the incidence of MH, the difference was statistically significant (odds ratio=5.70, 95% CI 2.22-14.61, P<0.05). Conclusion:BCVA and CFT could be improved by PPV combined total and fovea-sparing peeling of ILM for myopic foveoschisis; compared with complete ILM peeling, the incidence of MH was lower after foveal-sparing ILM peeling.

The macula is a critical anatomical structure for primates to acquire high-resolution spatial and color vision, with macula lesions posing a significant threat to patients' visual function and quality of life. Non-human primate (NHP) are the only mammals with a macular structure that is closest to that of humans, thus offering substantial value in the study of macular diseases. Currently, various methods, including spontaneous occurrence, gene editing, drug-induced, light-induced, and mechanical injury, can be employed to screen and establish NHP models for investigating conditions such as oculocutaneous albinism, achromatopsia, retinitis pigmentosa, age-related macular degeneration, and certain rare ocular syndromes. When constructing NHP models, due consideration should be given to other animal models to facilitate complementary research across different model systems. Additionally, leveraging the advantages of NHP and establishing genetically controlled NHP strains is a goal to strive for to achieve sustainable utilization of these resources in research.

Objective:To explore the clinical characteristics and genetic etiology of a Chinese Hui family with nanophthalmos.Methods:A pedigree investigation was performed.The clinical features and genetic etiology analysis were conducted in this Chinese family with nanophthalmos who first visited Beijing Tongren Eye Center in October 2005 and were followed up until October 2023.This family included 25 individuals of 4 generations, among which there were 3 patients.All the patients underwent medical history collection and comprehensive ophthalmological examinations, including visual acuity, intraocular pressure, slit-lamp microscope, IOLMaster, ultrasound biomicroscopy, color fundus photography, B-scan ultrasonography, visual field, etc.Genomic DNA was extracted from the 3 patients and 3 phenotypically normal individuals.Disease-causing genes were screened by whole-exome sequencing.Bioinformatic analysis and prediction of pathogenicity of candidate variants were conducted, followed by further validation by Sanger sequencing and co-segregation analysis.All the included subjects were informed of the purpose and methods of the study and signed an informed consent form.The study protocol was reviewed and approved by the Ethics Committee of Beijing Tongren Hospital, Capital Medical University (No.TRECKY2021-241).Results:Nanophthalmos in this family was inherited in an autosomal recessive manner.The proband and his two sisters were diagnosed with nanophthalmos based on clinical evaluation of typical phenotypes including the reduction of visual acuity, hyperpresbyopia, short ocular axis, shallow anterior chamber, narrow anterior chamber angle, high intraocular pressure, crowded optic disc, tortuous retinal vessel, etc.companied by angle-closure glaucoma, exudative retinal detachment and uveal effusion and other common complications.Compound heterozygous variants c. 1010_1021del (p.His337_Glu340del) and c. 1486G>A (p.Glu496Lys) were detected in MFRP gene in all three patients, and c. 1010_1021del, one of the biallelic variants was first reported.Both variants were rare in healthy populations and were co-segregated within this pedigree.According to the standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, the variants were predicted to have strong pathogenicity and were the genetic cause of the nanophthalmos in this pedigree. Conclusions:This study finds a novel pathogenic variant c.1010_1021del in a nanophthalmos pedigree.

RCBTB1 gene associated hereditary retinopathy is an extremely rare inherited retinal disease (IRD) discovered recently. The mutation of RCBTB1 gene can lead to a variety of IRD clinical phenotypes, such as early retinitis pigmentosa and delayed chorioretinal atrophy. The hereditary mode of RCBTB1 gene associated retinopathy is autosomal recessive. RCBTB1 gene plays an important role in maintaining mitochondrial function and anti-oxidative stress defense mechanism of retinal pigment epithelium cells. In the future, it is necessary to further determine whether there is a genotypic and phenotypic correlation in the age of onset of RCBTB1 gene associated retinopathy or multi-organ involvement, and evaluate the safety and efficacy of adeno-associated virus-mediated RCBTB1 gene replacement therapy in animal models, to explore the feasibility of gene replacement therapy and stem cell therapy.