Diabetic retinopathy (DR) is one of the microvascular complications of diabetes mellitus causing severe visual impairment, and it is the main cause of blindness in adults. Metabolic abnormalities play an important role in the occurrence and development of DR, including the abnormal levels of glucose metabolism, lipid metabolism, amino acid metabolism and purine metabolism, which indicate that there are disorders of phosphopentose pathway, arginine metabolism pathway, polyol pathway and ascorbic acid pathway in the progression of DR. Metabolomics has great advantages in exploring the pathogenesis and diagnosis of DR, helping to identify the characteristic metabolic changes of DR And discover potential biomarkers. However, the existing metabolomics studies on DR have some limitations, such as the potential biomarkers found in some studies are difficult to verify in other studies due to differences in race, age, gender and sample size. There are few studies on biomarkers at different stages of DR. Therefore, in the future, multi-center and large-scale clinical studies are needed to screen out biomarkers with practical clinical diagnostic value.
ObjectiveTo predict as well as bioinformatically analyze the target genes of has-miR-451. MethodsmiRBase, miRanda, TargetScan and PicTar were used to predict the target genes of hsa-miRNA-451. The functions of the target genes were demonstrated by Gene Ontology and pathway enrichment analysis. P < 0.05 was set as statistically significant. Results18 target spots of hsa-miRNA-451 were predicted by 3 databases or prediction software at least. The functions of the target genes were enriched in proliferation and development of epithelial cells and regulation of kinase activity (P < 0.05). Pathway analysis showed that transforming growth factor-beta signaling pathway, mitogen-activated protein kinase signaling pathway, epidermal growth factor signaling pathway, Wnt signaling pathway and mammalian target of rapamycin signaling pathway were significantly enriched (P < 0.05). Conclusionhsa-miRNA-451 might be involved in various signaling pathways related to proliferation and development of epithelial cells.
Diabetic macular edema (DME) is one of the main reasons causing blindness in patients with diabetic retinopathy. In recent years, with the recognition of the pathogenic role of vascular endothelial growth factor (VEGF) in DME, many clinical trials of intravitreal injection of anti-VEGF drugs have been carried out at home and abroad, proving that it has significant effects in improving visual acuity and reducing macular edema, and has become the first-line treatment of DME. However, there are still many challenges in routine clinical application of anti-VEGF drugs, such as frequent injections, insensitivity to treatment, and it is unclear whether repeated injections will cause damage to retina. The pathophysiological process of DME is very complicated, in addition to VEGF, there are many inflammatory factors and growth factors involved. Clinical trials of long-acting anti-VEGF agents, drugs of other targets and gene therapy are also being carried out. It is believed that with the in-depth research and progress of clinical trials, the gradual application of anti-VEGF drugs, other drugs and therapy in clinical practice are just around the corner, which is expected to provide more convenient and effective treatments for DME patients in the future.
Neurovascular unit (NVU) refers to a functional complex of neural cells and vasculature, which plays an important role in maintaining retinal homeostasis and matching metabolic demands. In physiological situation, retinal NVU mainly exerts two effects: (1) maintaining blood-retinal barrier for retinal homeostasis maintenance; (2) regulating local blood flow to meet metabolic and functional demands of the retina. The pathological changes in retinal diseases are reflected in each functional part of retinal NVU, including cell-cell connections, signal pathways, metabolic activities and cellular functions. However, the main pattern and manifestation of NVU impairment differs among retinal diseases due to different etiologies. At present, understanding on retinal NVU is still insufficient, and its clinical application is even more limited. Further application in the diagnosis and treatment of retinal diseases is an important direction for future research on NVU.
Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes, and it is the main cause of vision loss in diabetic patients. Angiopoietin (Ang), a superfamily of secreted proteins, is a vascular growth factor that regulates the stability of vascular environment, participates in angiogenesis and repair, and lipid metabolism. It plays an important role in the development of DR and has become a new target for the treatment of diabetic retinopathy. With the in-depth study of Ang and the research and development of various drugs for Ang, it is expected to bring new ideas and strategies for the treatment of DR in the future.
ObjectiveTo measure the macular retinal thickness of middle-aged and elderly myopic patients and examine the correlations between the macular retinal thickness and the axial length (AL), diopter, corrected visual acuity and gender. Methods Eight-five middle-aged and elderly myopic patients (96 eyes), including 43 females (52 eyes) and 42 males (44 eyes), with an average age of 63±6 years, were enrolled in this study. All subjects underwent a full ophthalmic examination including visual acuity, intraocular pressure, slit lamp, indirect ophthalmoscopy, OCT, refraction and diopter and A-scan ultrasound biometry. The patients were divided into three groups according to the AL and spherical equivalent degree (SED) that stands for diopter, including low and intermediate myopia group, high myopia group and super high myopia group. There were no significant differences in age (χ2=1.875), gender (χ2=0.667) and right/left eye distribution (χ2=0.375) among the 3 groups (P > 0.05), and significant differences were found in the AL (F=345.75), SED (F=239.05) and corrected visual acuity (F=3.679) among the 3 groups of patients (P < 0.05). SD-OCT was used to measure the total average macular thickness (TR), central subfield thickness, and the retina thickness in 4 quadrants of the inner and outer ring (IR/OR) of macular. Correlation between AL, SED, and corrected visual acuity with macular TR was analyzed by Pearson correlation analysis. Independent-Sample Test was used in TR comparison in different sex-group and macular retina area. ResultsThe retinal thickness of all the macular regions, except those at inferior and superior inner ring of macular, was significantly different among the 3 groups (F=6.794, 10.155, 5.861, 6.692, 12.081, 10.729, 5.137; P < 0.05).The retinal thickness of IR, OR and TR was significantly different among the 3 groups(F=7.370, 17.939, 15.553; P < 0.05). Superior inner macular thickness had no correlations with both AL and SED (r=-0.103, -0.098; P > 0.05). Inferior inner macular thickness had no correlations with AL, but had negative correlations with SED (r=-0.203, P < 0.05). The central subfield thickness (t=-2.082), temporal inner macular thickness (t=-2.564), superior inner thickness (t=-2.958), average inner macular thickness (t=-2.777) and TR (t=-2.400) was lower in females compared to males, and significant differences were existed (P < 0.05). ConclusionsIn our study, middle-aged and elderly myopic patients featured generally thinner macular retinal thickness, and the central subfield thickness, temporary and nasal inner macular thickness and all the quadrants of outer macular thickness was decreased significantly. Females are characterized by thinner central subfield thickness, inner macular thickness and total average macular thickness compared to males.
ObjectiveTo investigate the prevalence and risk factors of tessellation fundus (TF) among Tianjin Medical University students with different refractive statuses. MethodsA cross-sectional study. From September to December 2019, 346 students from Tianjin Medical University were randomly selected and underwent slit-lamp examination, non-cycloplegic auto-refraction, subjective refraction, best-corrected visual acuity, ocular biometric measurement, and non-dilation fundus photography. The differences in the prevalence of TF in basic characteristics and ocular biometric parameters were compared. Based on the equivalent spherical (SE), refractive status was divided into the non-myopia group (SE＞－0.50 D) and the myopia group (SE≤－0.50 D). The myopia group was further divided into mild myopia group (－3.00 D＜SE≤－0.50 D), moderate myopia group (－6.00 D＜SE≤－3.00 D), and high myopia group (SE≤－6.00 D). According to the axis length (AL), the subjects were divided into AL＜24 mm group, 24-26 mm group, and ＞26 mm group. The logistic regression was used to analyze the risk factors affecting TF. Trend tests were performed for each risk factor and TF. ResultsOf the 346 subjects, 324 (93.6%, 324/346) were myopia, of whom 73 (21.1%, 73/346), 167 (48.3%, 167/346), and 84 (24.3%, 84/346) were mild myopia, moderate myopia, and high myopia, respectively; 22 (6.4%, 22/346) were non-myopia. There were 294 (85.0%, 294/346) students with TF in the macula, including 9 (40.91%, 9/22), 58 (79.45%, 58/73), 145 (86.83%, 145/167), and 82 (97.62%, 82/84) in non-myopia, low myopia, moderate myopia, and high myopia group, respectively; 52 (15.0%, 52/346) students were without TF in the macula. There were statistically significant gender differences (χ2=4.47), SE (t=6.29), AL (t=－8.29), anterior chamber depth (Z=－2.62), lens thickness (Z=－2.23), and average corneal radius (Z=－3.58) between students with and without TF in the macula (P＜0.05). Spherical equivalent and axial length were independent risk factors for TF and its severity (P≤0.001). With an increasing degree of myopia, and increasing axial length, the risk of TF increased (P for trend＜0.001). ConclusionsThe prevalence of TF is 85.0% among Tianjin Medical University students. TF is detected in the fundus of no myopia, mild myopia, moderate myopia and high myopia. The degree of myopia is higher, the AL is longer, the possibility of TF is higher.
ObjectiveTo observe the effects of RasGRP4 gene deletion on the structure and function of the retina in diabetic mice, and to explore the mechanism of RasGRP4 in diabetic retinopathy (DR) by transcriptome sequencing in conjunction with bioinformatics analysis. MethodsA total of 12 male C57BL/6J mice were divided into normal group, diabetic group (DM group), with 6 mice in each group. Six male RasGRP4 knockout mice were uesd as RasGRP4 knockout diabetic group (DM-KO group). Mice in the DM group and DM-KO group were fed with high-fat diet combined with intraperitoneal injection of streptozotocin to establish diabetic model and body weight and blood glucose were monitored regularly. Three months after modeling, optical coherence tomography (OCT) was used to detect the retinal thickness. Electroretinography (ERG) was used to detect the function of the retina in mice under dark-adapted conditions. Total RNA was extracted from the retinas of the DM group and DM-KO group for transcriptome sequencing and bioinformatics analysis. The relative expression of IL-8, TGF-β, IFN-γ, NLRP3, Caspase-1, and IL-1β mRNA in retina were detected by real-time quantitative polymerase chain reaction (qRT-PCR). One-way analysis of variance was used to compare groups. ResultsThere was no statistically significant difference in blood glucose and body weight between mice in the DM group and DM-KO group (t=0.12、2.02、0.22、0.10、0.59、0.41、1.35、0.31、1.12、1.58、1.47、1.20、1.24、0.39、0.66、0.14, P＞0.05). Compared with the normal group, the retinal thickness and ganglion cell layer thickness were significantly decreased in the DM group, while the retinal thickness and ganglion cell layer thickness were significantly increased in the DM-KO group compared with the DM group, with statistical significance (F=30.43、7.81, P＜0.0001、0.01). Compared with the normal group, the a-wave and b-wave amplitudes were significantly decreased in the DM group, while the a-wave and b-wave amplitudes were significantly increased in the DM-KO group compared with the DM group, with statistical significance (F=16.46、35.58, P＜0.001、0.0001). Compared with the DM group, 184 differential genes (DEG) were screened in the DM-KO group, among which 39 up-regulated and 145 down-regulated genes were detected, respectively. The results of the MCODE plug-in analysis showed that Col1a2, Fbln1, Fbn1, Col6a3, Fmod, Ogn, Tgfb, Mfap4, Vcan, Nid2, and Col18a1 were core genes in the DEG. Cytohubba plug-in analysis showed that Col1a2, Mrc1, Cd47, Fbn1, Cybb, Cd163, Fbln1, Fmod, Adgre1, and Col6a3 were the core genes in DEG. The results of the GO functional enrichment analysis showed that DEG was mainly involved in hemoglobin complexes, MHC class II protein complex, apical plasma membrane, inflammasome complex, immunological synapse, response to bacterium, inflammatory response, immune system processe, response to hypoxia, and cell adhesion were significantly enriched. qRT-PCR results showed that compared with the normal group, the relative expression levels of IL-8, TGF-β, IFN-γ, NLRP3, Caspase-1, and IL-1β mRNA in the retina of mice in DM group were significantly increased, while the relative expression levels of IL-8, TGF-β, IFN-γ, NLRP3, Caspase-1, and IL-1β mRNA in the retina of mice in DM-KO group were significantly decreased compared with the DM group, with statistical significance (F=12.43、15.41、70.09、29.04、11.79、41.28, P＜0.01). Conclusion RasGRP4 deficiency plays a therapeutic role in the development of DR through inhibition of inflammatory factor secretion and NLRP 3 inflammasome pathway activation.