1.Research progress of circRNA in retinoblastoma
Pengxue WEI ; Jia LIANG ; Shijing WANG ; Dong FANG ; Shaochong ZHANG
Chinese Journal of Ocular Fundus Diseases 2024;40(6):478-484
Retinoblastoma (RB), the most common primary intraocular malignancy in infants and young children, poses a serious threat to visual function and the life of children when systemic metastasis occurs. Circular RNA (circRNA) is a recently discovered class of non-coding RNA that mainly functions as competitive endogenous RNA by regulating gene expression through competing with microRNA. circRNA can function as oncogenes or tumor suppressors, regulating various biological processes in RB cells, such as proliferation, migration, apoptosis, autophagy, and drug resistance, thereby providing new therapeutic targets for RB. In addition, the differential expression of circRNA in tumor tissues or exosomes is expected to be a potential biomarker for RB. Further studies and explorations are still needed for the functions and regulatory mechanisms of circRNA in RB to reveal their precise roles in organisms and potential clinical applications.
2.Structure and physiological function of internal limiting membrane and its role in related diseases
Jia LIANG ; Lu CHEN ; Shaochong ZHANG
Chinese Journal of Experimental Ophthalmology 2024;42(5):478-482
Internal limiting membrane (ILM) is a translucent homogeneous membrane composed of Müller cell basement membrane and a small number of glial cells.The alpha collagen, sulfate protein sugar and laminin in ILM play important roles in the development of retinal basement membrane and neurovascular structure and in the formation of retinal barrier.However, when pathological changes occur in its composition, structure and physical and chemical properties, it may cause the occurrence and development of many vitreoretinal diseases.At present, ILM peeling which is widely used in vitreoretinal diseases can effectively relieve the traction of residual vitreous cortex on retina and prevent postoperative epiretinal membrane formation, but there are still some problems such as retinal microstructure and physiological function damage.Therefore, some ILM-modified surgeries have been developed, including fovea-sparing ILM peeling, inverted ILM flap, and ILM transplantation technique.This article summarizes the physical and chemical properties, physiological functions, pathologic changes in ILM-related diseases and ILM-related surgical methods, with the goal of providing an advanced understanding of the ILM and aiding in clinical diagnosis and treatment.
3.Genetic analysis of a family with posterior segment microphthalmia-retinoschisis and drusen syndrome
Ting XIE ; Qingshan CHEN ; Jia LIANG ; Dong FANG ; Lu CHEN ; Shaochong ZHANG
Chinese Journal of Experimental Ophthalmology 2024;42(10):919-925
Objective:To analyze the clinical phenotypes and genotypes of a family with posterior segment microphthalmia-retinoschisis and drusen syndrome.Methods:A pedigree investigation study was conducted.A family with four members across two generations treated at Shenzhen Eye Hospital in July 2021 was enrolled.Detailed ophthalmic examinations, including best corrected visual acuity (BCVA), intraocular pressure, slit-lamp microscopy, color fundus photography, optical coherence tomography (OCT), anterior segment OCT, fundus fluorescein angiography (FFA), and visual field tests were performed in the four members.Peripheral venous blood samples were collected from members for whole exome sequencing and data analysis.The pathogenicity of novel variant sites was assessed according to the ACMG guidelines.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Shenzhen Eye Hospital (No.22KYPJ018).Written informed consent was obtained from each subject or the guardian.Results:The proband is a 14-year-old female with high hyperopia since childhood, BCVA of + 9.75 DS-0.75 DC×150°=0.9 and + 11.75 DS-1.25 DC×30°=0.7, corneal transverse diameters of 12.1 and 12.2 mm, anterior chamber depths of 2.56 and 2.92 mm, lens thicknesses of 3.92 and 3.94 mm, and axial lengths of 17.47 and 17.01 mm in the right and left eyes, respectively.Fundus photography revealed diffuse yellow-white drusen-like lesions with unclear borders in the mid-peripheral retina, while OCT showed retinoschisis in the inner nuclear layer and homogeneous mound-like elevations with hyperreflective dense spots under the retinal pigment epithelium.FFA demonstrated diffuse punctate transilllumination of the mid-peripheral retina in both eyes, and visual field tests revealed a general decrease in visual acuity.The proband's 8-year-old brother exhibited similar signs to the proband.The consanguineously married parents were phenotypically normal.Whole exome sequencing identified compound heterozygous mutations in the membrane frizzled-related protein ( MFRP) gene in the proband and her brother, c.1150_1151insC (p.His384Profs*8) in exon 5 and c. 498_499insC (p.Asn167Glnfs*34) in exon 10.The father carried the c. 498_499insC mutation, while the mother carried the c.1150_1151insC mutation.Both were frameshift mutations predicted to alter gene function.These novel mutations had not been reported in the ESP, 1 000 Genomes (Phase 3), or ExAC databases, indicating they are novel variants.The variants co-segregated with the disease and both were classified as pathogenic according to ACMG guidelines.Based on the clinical and genetic findings, the family was diagnosed with posterior segment microphthalmia-retinoschisis and drusen syndrome, inherited in an autosomal recessive manner. Conclusions:The MFRP gene mutations c. 1150_1151insC and c. 498_499insC are the pathogenic variants for the posterior segment microphthalmia-retinoschisis and drusen syndrome in this family, and these compound heterozygous mutations are reported for the first time.
4.Opinion on the development and research status of intelligent ophthalmology in China
Di GONG ; Wangting LI ; Xiaomeng LI ; Cheng WAN ; Yongjin ZHOU ; Yanwu XU ; Shaochong ZHANG ; Weihua YANG
International Eye Science 2024;24(3):448-452
This paper provides a comprehensive analysis of the current state of intelligent ophthalmology in China, including technological advancements, academic exchange platforms, policy support, future challenges, and potential solutions. Technologically, remarkable progress have been made in various areas of intelligent ophthalmology in China, including diabetic retinopathy, fundus image analysis, and crucial aspects such as quality assessment of medical artificial intelligence products, clinical research methods, technological evaluation, and industrial standards. Researchers are constantly improving the safety and standardization of intelligent ophthalmology technology by formulating clinical application guidelines and standards. Academic exchange platforms have been established to provide extensive collaboration opportunities for professionals across diverse fields, and various academic journals serve as publication platforms for intelligent ophthalmology research. Regarding public policy, the Chinese government has not only established a supportive policy environment for the advancement of intelligent ophthalmology through various documents and regulations, but provided a legal basis and management framework. However, there are still challenges to overcome, such as technological innovation, data privacy and security, outdated regulations, and talent shortages. To tackle these issues, there is a requirement for increased technological research and development, the establishment of regulatory frameworks, talent cultivation, and greater awareness and acceptance of new technologies among patients. By comprehensively addressing these challenges, intelligent ophthalmology in China is expected to continue leading the industry's global development, bringing more innovation and convenience to the field of ophthalmic healthcare.
5.Metabolomics study of kidney tissue in a mouse model of oxygen-induced retinopathy
Lijun DONG ; Hui QI ; Yuhang YANG ; Xingxing MAO ; Guoming ZHANG ; Shaochong ZHANG ; Hetian LEI
Chinese Journal of Experimental Ophthalmology 2024;42(1):19-28
Objective:To explore the effects of hyperoxic environments on renal metabolites to understand the potential mechanisms that contribute to pathologic retinal vascular neovascularization and renal injury through metabolomic studies in a mouse model of oxygen-induced retinopathy (OIR) model.Methods:Sixteen C57/B6J mice pups born to day 7 (P7) were randomly and equally divided into an OIR model group and a normal control group using a randomized numerical table of mother mice.Mice were reared standardly from birth until day 7 (P7), then mice and their mother mice in the OIR group were placed in a hyperoxic (75±2)% chamber until day 12 (P12) and then reared normally.Mice in the normal control group were reared normally throughout.Mice in two groups were killed by carbon dioxide euthanasia on postnatal day 17 (P17). The mice retinal wholemount from the two groups were made and stained with isolectin B4 (IB4) to observe the morphology of retinal vessels, central non-perfusion area and pathological neovascularization.The kidney tissue of P17 mice was analyzed by liquid chromatograph mass spectrometer.After anticoagulant treatment, the whole blood of mice was centrifuged and precipitated, and the obtained plasma without cellular components was analyzed by targeted metabonomics.Mass spectral information was interpreted using metabolomics data processing software Progenesis QI v2.3.Overall differences in metabolic profiles were distinguished by unsupervised principal component analysis and orthogonal partial least squares analysis (OPLS-DA). The fold change and P values of metabolites were compared between the two groups.The variable importance of projection value>1 and P value<0.05 was used to screen out differential metabolites.Metabolic pathway enrichment analysis of differential metabolites was performed based on the KEGG database.The feeding and use of animals were strictly in accordance with the requirements of the Ethics Committee of Jinan University, and the research protocol was reviewed and approved by the Ethics Committee of Jinan University (No.20200401-54). Results:The IB4 staining of retinal wholemounts showed that the retinal blood vessels were evenly distributed in the P17 mice from control group.The peripheral retinal vessels were tortuous and disordered with a large non-perfusion area in central region in P17 mice from OIR group, and a large number of neovascularization clusters were formed at the junction of the nonperfusion area and the vascular area of the retina, showing strong fluorescent staining.The relative area of retinal nonperfusion area in OIR group was (25.16±3.50)%, which was significantly larger than (0.63±0.30)% in normal control group ( t=12.07, P<0.001). The OPLS-DA parameter R2X cum (0.578), interpretation rate R2Y cum (0.978) and prediction rate Q2 cum (0.857) values were all greater than 0.5, indicating that the OPLS-DA model had a good predictive ability.A total of 26 main differential metabolites were found, among which 17 were up-regulated and 9 were down-regulated, including glycerophospholipids (PC 20∶4(5Z, 8Z, 11Z, 14Z)/0∶0, PC 22∶6(4Z, 7Z, 10Z, 13Z, 16Z, 19Z)/0∶0, PC 14∶1(9Z)/20∶2(11Z, 14Z), PE P-18∶0/20∶4(6E, 8Z, 11Z, 14Z)(5OH[S]), amino acid metabolites (arginine, ornithine, pipecolic acid, and hydroxylysine), purines (guanine, hypoxanthine, hydroxypurinol), and fatty acids (methyl 15-palmitate, 2, 6, 8, 12-tetramethyl-2, 4-tridecadien-1-ol), and so on.Differential metabolites were mainly enriched in ABC transporters (L-arginine, taurine, inositol, adenosine, N-acetyl-D-glucosamine, L-glutamine), aminoacyl-tRNA biosynthesis (L-isoleucine, L-proline, L-arginine, L-histidine, L-glutamine), arginine biosynthesis (L-arginine, L-ornithine, L-glutamine) metabolic pathways.The plasma targeted metabonomics showed that the differential amino acid metabolites were mainly enriched in metabolic pathways such as aminoacyl-tRNA biosynthesis, arginine biosynthesis and metabolism, and ABC transporters. Conclusions:ABC transporter, aminoacyl-tRNA biosynthesis, and arginine biosynthesis metabolic pathways in OIR mice may participate in the pathological changes of renal injury and neovascularization in retinopathy of prematurity.
6.Research progress on optical coherence tomography-based morphological changes in the fundus of patients with chronic obstructive pulmonary disease
Yingying DIAO ; Weihua YANG ; Dong FANG ; Wangting LI ; Shaochong ZHANG
International Eye Science 2024;24(10):1563-1568
Chronic obstructive pulmonary disease(COPD)is a group of lung diseases characterized by persistent airflow limitation, often accompanied by chronic hypoxia. This chronic hypoxia can lead to structural and functional changes in the walls of blood vessels throughout the body, causing vascular injury and altered vascular reactivity. The retina and choroid are key ocular structures with rich blood supply and are particularly prone to microstructural changes due to ischemia and hypoxia. Optical coherence tomography(OCT), an ideal tool for observing these microstructural changes, serves as a non-invasive method for assessing retinal microstructures and microvascular pathology. Currently, there is a lack of comprehensive reviews summarizing OCT-based morphological changes in the eyes of COPD patients. This paper provides an in-depth review of existing studies on ocular OCT in COPD patients, focusing on structural and blood flow changes in the retina and choroid. The primary goal of this review is to summarize the impact of COPD on ocular microstructures, explore the underlying mechanisms of these morphological changes, and offer new perspectives for assessing eye diseases in COPD patients.
7.Equity of resource allocation in ophthalmology departments of medical institutions in Shenzhen City
Jingfeng MU ; Meizhou LIU ; Shaochong ZHANG
Journal of Preventive Medicine 2023;35(3):267-270
Objective :
To investigate equity of resource allocation in ophthalmology departments of medical institutions in Shenzhen City, so as to provide insights into the optimization of resource allocation in ophthalmology departments in Shenzhen City.
Methods :
The numbers of beds and ophthalmologists in ophthalmology departments of medical institutions in Shenzhen City were collected through the Shenzhen Health Statistical Yearbook 2019. The distribution of resources and equity of resource allocation were evaluated in ophthalmology departments of Shenzhen City using Lorenz curve and Gini coefficient.
Results :
There were 5.95 beds and 4.62 ophthalmologists in ophthalmology departments per 100 000 permanent residents in Shenzhen City in 2019. There were 13.35 beds and 9.51 ophthalmologists in ophthalmology departments per 100 000 permanent residents within the former special zone (Luohu, Futian, Nanshan and Yantian districts), and 2.17 beds and 2.13 ophthalmologists in ophthalmology departments per 100 000 permanent residents outside the former special zone (Guangming, Baoan, Longhua, Longgang, Pingshan districts and Dapeng New Area). The Gini coefficients of beds and ophthalmologists in ophthalmology departments were 0.348 and 0.243 by permanent residents in Shenzhen City, 0.386 and 0.386 within the former special zone and 0.086 and 0.012 outside the former special zone, respectively. The Lorenz curves of beds and ophthalmologists in ophthalmology departments were closer to the equity line outside the former special zone in relative to within the former special zone.
Conclusion
The gross number of beds and ophthalmologists remains to be increased in ophthalmology departments of medical institutions in Shenzhen City, and the equity of regional resource allocation is poor, which is mainly characterized by resource scarcity in ophthalmology departments outside the former special zone.
8.Research progress of hydroxychloroquine retinopathy
Jia LIANG ; Dong FANG ; Lu CHEN ; Ting XIE ; Pengxue WEI ; Shaochong ZHANG
Chinese Journal of Ocular Fundus Diseases 2023;39(6):515-519
Hydroxychloroquine is widely used in a variety of autoimmune diseases. However, long-term use of hydroxychloroquine can cause severe retinopathy, which has a complex pathogenic mechanism and diverse clinical manifestations, mainly manifested as photoreceptor and retinal pigment epithelial damage and irreversible vision loss. Identifying damage before retinitis pigment epithelium lesions preserve central vision, so early detection is crucial to slow disease progression and reduce vision loss. The development of multimodal imaging technology and the issuance of the latest treatment guidelines provide a powerful tool for the early screening and treatment of hydroxychloroquine retinopathy. Proficient in the latest guidelines for the treatment of hydroxychloroquine can better guide clinicians to do a good job in disease screening and management, recommend risks, safe dosages and appropriate screening procedures to patients and strengthen the prevention of hydroxychloroquine retinopathy, which will help save the vision of more patients and reduce the waste of medical resources.
9.The relationship between sarcopenia and the maximum diaphragmatic excursion on ultrasound in the elderly
Bin ZENG ; Shaochong HE ; Guiying LIANG ; Yakang LIU ; Longping WANG ; Mingsheng ZHANG
Chinese Journal of Geriatrics 2022;41(2):196-200
Objective:To investigate the relationship between sarcopenia and the maximum diaphragm excursion(Dmax)observed on ultrasound in the elderly.Methods:Elderly volunteers(age≥60 years)were recruited from family members of patients at Guangdong Provincial People's Hospital.Their Dmax during forced inhalation was measured via ultrasound.The parameters for the diagnosis of sarcopenia included the appendicular skeletal muscle mass index(ASMI), handgrip strength and usual gait speed.We compared the differences in physical characteristics, pulmonary ventilation, physical performance and Dmax between patients with and without sarcopenia, and evaluated the relationship between sarcopenia and DEmax in the elderly via linear regression.Results:A total of 145 elderly volunteers[age(69.47±5.15)years]were included, and 28(19.31%)were diagnosed with sarcopenia.Body weight, ASMI, maximum inspiratory pressure(Pinmax), maximal power output(Wmax)and Dmax of patients with sarcopenia were significantly lower than those of patients without sarcopenia(all P<0.05).Dmax in the elderly was correlated with sex, height, ASMI, handgrip strength, usual gait speed, Pinmax and Wmax( r=0.181, 0.130, 0.322, 0.373, 0.401, 0.134, and 0.388, P=0.012, 0.037, 0.009, 0.002, 0.022, 0.009, and 0.002, respectively).After adjusting for sex, age, height and forced vital capacity(FVC), there was still a negative correlation between sarcopenia and Dmax in the elderly( β=-0.310, P=0.021). Conclusions:Dmax is related to Pinmax and physical performance in the elderly, and sarcopenia increases the risk of decline in the maximum diaphragm excursion in the elderly as observed on ultrasound.
10.Bone morphogenetic protein 4 promotes the proliferation and migration of retinal vascular endothelial cells
Juping LIU ; Yaru HONG ; Xuyang YAO ; Zhe ZHANG ; Shaochong BU ; Hui LI ; Jingjing CAO ; Xiaomei BAI ; Xiaorong LI ; Lijie DONG
Chinese Journal of Ocular Fundus Diseases 2022;38(4):304-309
Objective:To observe the effect of bone morphogenetic protein 4 (BMP4) on the proliferation and migration of human retinal microvascular endothelial cells (hRMEC) under oxidative stress.Methods:The hRMEC cultured in vitro were divided into control group, 4-hydroxynonenal (HNE) treatment group (4-HNE group), 4-HNE+BMP4 group (BMP4 group). Cell culture medium of 4-HNE treatment group was added with 10 μmmol/L 4-HNE; cell culture of BMP4 group was cultured with 10 μmmol/L 4-HNE, and after stimulation for 6 h, 100 ng/ml recombinant human BMP4 was added. The effects of 4-HNE and BMP4 on hRMEC viability was detected by thiazole blue colorimetric method. The effects of 4-HNE and BMP4 on cell migration was determined by cell scratch test. The relative expression of BMP4 mRNA in the cells of the control group and 4-HNE treatment group and the mRNA expression of the control group, the fibronectin (FN) of BMP4 group, laminin (Laminin), α-smooth muscle contractile protein (α-SMA), and collagen type Ⅰ (Collagen Ⅰ), vascular endothelial growth factor (VEGF), and connective tissue growth factor (CTGF) were detected by real-time quantitative polymerase chain reaction (qRT-PCR). Western blot was used to detect the relative expression of BMP4 protein in the control group and 4-HNE group. The control group and 4-HNE group were compared by t test. Results:Compared with the control group, cell viability ( t=12.73, 16.26, P=0.000 2, <0.000 1), cell migration rate ( t=28.17, 37.48, P<0.000 1, <0.000 1) in 4-HNE group and BMP4 group were significantly increased, and the difference was statistically significant; the relative expression of BMP4 mRNA and protein in the 4-HNE group was significantly increased, and the difference was statistically significant ( t=16.36, 69.35, P=0.000 1, <0.000 1). The qRT-PCR test results showed that compared with the control group, the relative expression of VEGF, FN, Laminin, α-SMA, Collagen Ⅰ, and CTGF mRNA in the cells of the BMP4 group was significantly increased, and the difference was statistically significant ( t=10.61, 17.00, 14.85, 7.78, 12.02, 10.61, P=0.0004, <0.000 1, 0.000 1, 0.001 5, 0.000 1, 0.000 4). Conclusion:BMP4 can induce the proliferation and migration of hRMEC; it can also regulate the expression of angiogenesis factors and fibrosis-related factors in hRMEC.


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