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.
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.
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.
Hereditary ocular fundus disease is an important cause of irreversible damage to patients' visual acuity. It has attracted much attention due to its poor prognosis and lack of effective clinical interventions. With the discovery of a large number of hereditary ocular fundus genes and the development of gene editing technology and stem cell technology, gene and stem cell therapy emerged as the new hope for curing such diseases. Gene therapy is more directed at early hereditary ocular fundus diseases, using wild-type gene fragments to replace mutant genes to maintain existing retinal cell viability. Stem cell therapy is more targeted at advanced hereditary ocular fundus diseases, replacing and filling the disabled retinal cell with healthy stem cells. Although gene and stem cell therapy still face many problems such as gene off-target, differentiation efficiency, cell migration and long-term efficacy, the results obtained in preclinical and clinical trials should not be underestimated. With the emergence of various new technologies and new materials, it is bound to further assist gene and stem cell therapy, bringing unlimited opportunities and possibilities for the clinical cure of hereditary ocular fundus diseases.
Objective To observe the expression of genes related to hereditary retinal diseases (IRD) in human microglia (hMG). MethodsA experimental study. Efficient differentiation of human induced pluripotent stem cells (iPSC) into hMG. Identification of octamer-binding transcription factor 4 (OCT4), sex-determining transcription factor 2 (SOX2), Nanog homeobox (NANOG), stage-specific embryonic antigen-4 (SSEA4), alpha-fetoprotein (AFP), α-smooth muscle actin (α-SMA) as markers associated with iPSC dryness and pluripotency by immunofluorescence staining Glial fibrillary acidic protein (GFAP); hMG associated marker transmembrane protein 119 (TMEM119), purinergic receptor P2Y12 (P2RY12), and allograft inflammatory factor 1 (IBA1). The proportion of CD11b+ and CD45+ cells was detected by flow cytometry. Mature hMG was collected and stimulated with lipopolysaccharide for 0, 4, 8 and 12 h, and were divided into groups 0 h, 4 h, 8 h and 12 h, respectively. Total RNA samples from the 4 groups were extracted for transcriptome sequencing, and the persistently significant differentially expressed genes (DEG) were screened. Real-time quantitative polymerase chain reaction (qPCR) was used to verify and analyze the expression of DEG mRNA. The two-tailed Student t test was used for comparison between the two groups. ResultsiPSC expressed the dry related markers OCT4, SOX2, NANOG and SSEA4, and differentiated into endoderm, mesoderm and ectoderm, expressing the corresponding markers AFP, α-SMA and GFAP, respectively. iPSC formed embryoid bodies under specific culture conditions, and then differentiated into hMG, and hMG expressed related markers TMEM119, P2RY12 and IBA1 by immunofluorescence staining. The double positive ratio of CD11b+ and CD45+ was > 95%. Transcriptomic analysis showed that the expression of 18 DEG in hMG stimulated by LPS was changed. qPCR test results showed that compared with group 0 h, mRNA expressions of Toll-like receptor 4 (TLR4), phosphoglycerate kinase 1, disintegrin and metallopeptidase domain 9 (ADAM9) in LPS stimulated group 4 h were significantly increased (t=25.43, 15.54, 6.26; P＜0.01). The mRNA expression levels of MER proto-oncogene tyrosine kinase (MERTK), non-hydrolase domain containing lysophospholipase 12 (ABHD12), retinal dehydrogenase 11 (RDH11), DNA damage autophagic regulator 2 (DRAM2) decreased (t=5.94, 14.14, 8.21, 6.97; P＜0.01), and the differences were statistically significant. Compared with group 0 h, mRNA expressions of RDH11, MERTK, ABHD12, DRAM2 and ADAM9 in group 8 h stimulated by LPS were significantly decreased, with statistical significance (t=25.97, 5.47, 43.97, 38.40, 3.84; P＜0.05). Compared with the group 0 h, the mRNA expressions of TLR4, ADAM9, MERTK, ABHD12, RDH11 and DRAM2 in the 12 h stimulated group were significantly decreased, and the differences were statistically significant (t=6.39, 46.11, 5.34, 14.14, 25.97, 25.65; P＜0.05). ConclusionIRD-related genes may be involved in the occurrence and development of IRD by regulating the function of hMG.
Lattice retinal degeneration is a common peripheral retinal degenerative condition and is widely recognized as a significant precursor to retinal detachment, resulting in severe visual loss. Recent advances in deep learning technologies have driven the development and adoption of automated screening systems for lattice retinal degeneration using ultra-widefield fundus imaging. These systems have demonstrated notable success in large-scale screening of peripheral retinal diseases, offering valuable support for the early identification and risk stratification of lattice degeneration. Currently, retinal laser photocoagulation remains the mainstay treatment for lattice degeneration. This intervention effectively mitigates the risk of rhegmatogenous retinal detachment. However, controversies persist regarding the optimal selection of treatment candidates and the evaluation of therapeutic efficacy. In the future, the continuous evolution of imaging analysis techniques and artificial intelligence holds promise for the development of personalized and precision-based intervention strategies. Such advancements are expected to provide more robust evidence to guide the diagnosis and treatment of lattice retinal degeneration, ultimately improving patient outcomes.
Alzheimer's disease (AD) is a neurodegenerative disorder with insidious onset and poor prognosis, and it is the primary cause of senile dementia. Its early diagnosis is challenging, and existing methods mostly rely on high-cost and invasive examinations. As an integral part of the central nervous system, the retina provides a non-invasive and efficient observation window for AD diagnosis. In recent years, with the development of ophthalmic imaging technologies such as optical coherence tomography, optical coherence tomography angiography, and hyperspectral imaging, a growing number of studies have revealed that AD patients exhibit retinal structural changes, structural and functional abnormalities of retinal blood vessels, and that amyloid-beta and Tau deposits can be detected via specific imaging methods—suggesting that these changes may occur prior to brain lesions. Meanwhile, the integrated analysis of multimodal imaging shows promising prospects in identifying retinal biomarkers and predicting AD risk, demonstrates the significant potential of retinal imaging technology in the early screening, diagnosis, and disease progression monitoring of AD, and provides a new source of biomarkers and potential clinical applications for AD research.
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.
Diffuse choroidal retinal atrophy (DCA) is a type of myopic macular disease that presents with yellowish-white atrophic changes at the posterior pole of the eyeball. DCA is an important critical feature in the diagnosis of pathological myopia. Early intervention and treatment of this disease are of great significance in delaying the progression of pathological myopia and reducing the impairment of visual function. Ophthalmic imaging data can be used to diagnose the disease, and color fundus photography is the most simple and intuitive. Choroidal thickness is also a key indicator in the diagnosis of DCA, but the diagnostic critical value of choroidal thickness has not been clearly defined. With the development and popularization of artificial intelligence technology, the analysis of lesion imaging data is more objective and accurate. In the future, it is expected to actively establish a standard quantitative evaluation system for DCA by means of artificial intelligence to achieve early detection, early diagnosis and early treatment of pathological myopia.
ObjectiveTo 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. MethodsA 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. ResultsIn 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). ConclusionBCVA 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.