Objective To investigate the molecular mechanisms by which the long non-coding RNA (lncRNA) MIR223HG affects the proliferation, migration and apoptosis of lung adenocarcinoma cells. MethodsDNA damaging agent Zeocin was used to treat human embryo lung cell (MRC-5) and lung cancer cell (A549 and H1299), and the expression of MIR223HG was tested by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Moreover, the ataxia-telangiectasia mutated (ATM) protein and ATM pathway downstream factor Cell cycle checkpoint kinase 2 (Chk2), p53 tumor suppressor protein (p53) in the lung cancer cell (A549 and H1299) with Zeocin were also tested by qRT-PCR. Cell transfection and Transwell migration assay, colony formation assays, apoptosis assays were performed to verify the role of ATM in the expression of MIR223HG in lung adenocarcinoma. ResultsThe expression of MIR223HG was reduced markedly in the lung cancer cells (A549 and H1299) compared with human embryo lung cell (MRC-5) after treated with Zeocin. ATM protein and its downstream factors Chk2, p53 involved in the process, and ATM regulated the expression of MIR223HG in the lung cancer cells with Zeocin. Futhermore, ATM joined in the processes that MIR223HG regulated the lung cancer cells proliferation, migration and apoptosis. Conclusions The expression of MIR223HG is related to the DNA damage response in the lung cancer, and MIR223HG regulates lung cancer cells proliferation, migration and apoptosis by ATM/Chk2/p53 pathway. MIR223HG may be a potential therapeutic target for lung adenocarcinoma treatment.
Cardiovascular disease is a severe threat to human health and life. Among many risk factors of cardiovascular disease, genetic or gene-based ones are drawing more and more attention in recent years. Accumulated evidence has demonstrated that the loss or mutation of ataxia telangiectasia mutated (ATM) gene can result in DNA damage repair dysfunctions, telomere shortening, decreased antioxidant capacity, insulin resistance, increased lipid levels, etc., and thus can promote the occurrence of cardiovascular risk factors, such as aging, atherosclerosis and metabolic syndrome. In this review, we discusses the possible mechanisms between ATM gene and cardiovascular risk factors, which could be helpful to the related research and clinical application.
Adult Coats disease is characterized by abnormal expansion of retinal capillaries, often accompanied by massive lipid exudation and exudative retinal detachment. Unlike Coats disease in young children, adult Coats disease is mostly limited to peripheral retina, with slow progress and better prognosis. Adult Coats disease should be identified with Coats-like diseases such as exudative age-related macular degeneration, diabetic retinopathy, obsolete retinal vein occlusion, idiopathic macular telangiectasia 1, obsolete posterior uveitis, retinal vasculitis, or acute retinal necrosis. Because the pathogenesis of Coats disease is not clear, it lacks specific treatment measures for the cause of disease. The purpose of simple or combined laser photocoagulation, freezing, vitreous intravitreal injection against vascular endothelial growth factor drugs or triamcinolone and surgery is to eliminate abnormal blood vessels and exudation, maintain visual function, which can also improve retinal detachment and prevent neovascular glaucoma and other complications. To explore the similarities and differences of adult Coats disease with Coats disease in young children, to further promote the study of the pathogenesis of adult Coats disease and to provide new targets for its treatment are the direction of future research.
Coats disease is a relatively rare and idiopathic disorder characterized by retinal telangiectasia and massive intra-retinal and (or) sub-retinal lipid accumulation, resulting in complications including retinal detachment and neovascular glaucoma. Previous reports have revealed that Coats disease can be associated with other disorders, especially some inherited diseases, such as retinitis pigmentosa (RP) and facioscapulohumeral muscular dystrophy (FSHD). Coats disease associated with other inherited disorders is generally called Coats-like retinopathy, which has some unique features that differs from the classic Coats disease, for example there is no sex and age preference, more bilateral cases, more severe cases and more genetic factors involved. Patients of Coats-like retinopathy with RP and FSHD may have mutations in Crumbs homologue gene 1 and D4Z4 genes.
Retinopathy of prematurity, familial exudative vitreoretinopathy and Coats disease are the most common neonates and infants retinal vascular diseases, which may lead to severe visual damage because of either tractional retinal detachment caused by the proliferation of pathogenic neovascularization, or exudative retinal detachment due to the extremely leakage from abnormal retinal vessels. Classic treatment is retinal laser photocoagulation which could destroy these abnormal vessels or reduce non vascular areas to diminish the growth of new vessels, however the side effects induced by laser it self such as visual field damage, hemorrhage, retinal tear, fail to control the progression of the disease make the laser treatment hard to improve the vision of these young patients. Anti-vascular endothelial growth factor (VEGF) agents have been widely applied in various adult retinal and choroidal vascular diseases, they are even possible to replace the pan retinal photocoagulation in proliferative diabetic retinopathy, while there are still many unsolved problems in the applying in neonates and infants retinal vascular diseases, like dosage, timing, retreatment and systemic side effects. We should realize the importance of selecting the laser photocoagulation and anti-VEGF for neonates and infants retinal vascular diseases.
ObjectiveTo study the effects and outcomes of green diode laser therapy under indirect ophthalmoscope in the treatment of juvenile Coats disease. MethodsNineteen juvenile Coats disease patients (19 eyes) well enrolled in this study. Average age at presentation was 73.5 months (27-146 months). Best corrected visual acuity (BCVA) was ≥0.1 in 7 eyes; 0.01 to 0.09 in 8 eyes; counting finger in 3 eyes and light perception in 1 eye. The macular of all eyes was involved. There were 3 eyes with macular exudative retinal detachment, 4 eyes with sub-macular fibrosis, 1 eye with macular atrophy. Exudative area was more than two quadrants in 17 eyes, and less than two quadrants in 2 eyes. The abnormal blood vessels located in the superior or nasal-superior retina (2 eyes) or inferior or temple-inferior area (17 eyes). Exudative retinal detachment occurred in 13 eyes, in which macular was not involved in 10 eyes, and macular was involved in 3 eyes. All patients were treated with green diode laser (532 nm) ablation therapy under general anesthesia and indirect ophthalmoscope to areas of the retina telangiectasia. 3 patients received a single intravitreal 2 mg triamcinolone injection (IVTA). Average follow-up was 18.5 months (6-51 months). Main outcome measures included visual acuity, retinal vascular abnormalities, subretinal exudates and exudative retinal detachment. ResultsAmong 3 patients treated with IVTA, one needed cataract extraction and one needed pre-retinal membrane peeling surgery. After laser photocoagulation, resolution of telangiectasia lesions was achieved in all patients at the end of follow-up. Exudation was resolved in 8 eyes, reduced in 9 patients and no change in 2 eyes. Exudative detachment was resolved in 8/13 eyes, reduced in area in 3/13 eyes and no change in 2 eyes. There were 9 eyes with sub-macular fibrosis and 3 eyes with macular atrophy at the end of follow-up. The visual acuity was stable in most cases. BCVA was ≥0.1 in 6 eyes; 0.01 to 0.09 in 11 eyes; counting finger in 1 eyes and light perception in 1 eye. Compared to the normal eyes, eyes with Coats disease tended to be more hyperopic (t=3.6,P=0.003) and astigmatic (t=3.6, P=0.004), but no correction were needed for these refractive errors. ConclusionsGreen diode laser therapy under indirect ophthalmoscope can be an effective treatment for juvenile Coats disease with little complications. IVTA can be helpful, but must be used with cautions as it can induce some complications.
ObjectiveTo observe the effect of local retinal laser photocoagulation (local photocoagulation) on Coats disease.MethodsA retrospective clinical study. From January 1, 2006 to August 1, 2020, 48 patients (48 eyes) who were diagnosed as Coats disease and received focal photocoagulation at The Eye Hospital Affiliated to Wenzhou Medical University were included in the study. Among them, there were 40 males (40 eyes) and 8 females (8 eyes). The average age was 32.46±22.41 years old. Nine eyes were in stage 2A, and 39 eyes were in stage 2B. All affected eyes underwent best corrected visual acuity (BCVA), color fundus photography and fluorescein fundus angiography (FFA).The BCVA was carried out using a standard logarithmic visual acuity chart, which was converted into the logarithmic minimum angle of resolution (logMAR) visual acuity during statistics. According to age, patients were divided into the adolescent group (age≤ 20 years old) and the adult group (age＞21 years old), with 18 eyes in 18 cases and 30 eyes in 30 cases, respectively. In the adolescent group, 18 eyes of 18 cases were all male; the average age was 11.17±3.31 years; the average logMAR BCVA was 0.83±0.60. Among the 30 patients in the adult group, 22 patients were male and 8 patients were female. the average age was 49.26±15.26 years old; the average logMAR BCVA was 0.82±0.59. All the affected eyes were treated with focal photocoagulation. Laser parameters were as followed: wavelength 577 nm, spot diameter 500 μm, exposure time 0.5 to 0.7 s, spot intensity level Ⅲ. FFA was FFA was performed 3 to 4 months after the first laser photocoagulation, and laser treatment was repeated as needed. The average follow-up after first treatment was 36.88±36.92 months. The changes in BCVA, abnormal blood vessels in the fundus, and hard exudation were observed.ResultsAmong 48 eyes, 36 eyes (75.00%, 36/48) received multiple local photocoagulation treatments. At the last follow-up, 36 eyes (75.00%, 36/48) had an improved or stable vision, and 17 eyes (35.42%, 17/48) had BCVA ≤ 0.32 logMAR units (≥ 0.5). The average logMAR BCVA of eyes in the adolescent group was 0.66±0.54, which was higher than the baseline, but the difference was not statistically significant (Z=－1.126, P=0.260). The average logMAR BCVA of the eyes in the adult group was 0.96±0.79, which was lower than the baseline, but the difference was not statistically significant (Z=－0.482, P=0.630). Among 48 eyes, abnormal blood vessels were completely or partially occluded in 42 eyes (87.50%, 42/48); of which, 29 eyes were completely occluded (60.42%, 29/48), and 13 eyes were partially occluded (27.08%, 13/48)). The hard exudation at macula or peripheral retina were completely absorbed or obviously absorbed in 40 eyes (83.33%, 40/48); among them, the complete and obvious absorption were 11 (22.92%, 11/48) and 29 (60.42%, 29/48) eyes.ConclusionThe treatment of focal photocoagulation with a larger spot, long exposure and weak level Ⅲ spot can effectively seal abnormal blood vessels in the eyes of Coats disease,reduce hard exudation and improve or stabilize vision.
ObjectiveTo investigate the efficacy and safety of traditional laser photocoagulation, laser combined with intravitreal injection of anti-vascular endothelial factor (anti-VEGF) drugs and intravitreal injection of anti-VEGF drugs alone in Coats disease. MethodsThe patients diagnosed as Coats disease stage 2B-3A2 in Department of Ophthalmology, Eye and ENT Hospital of Shanghai Medical College of Fudan University from December 2016 to November 2019 were included in this study. Patients were divided into three groups, including laser group, combined group and drug group, according to the different treatment. In the laser group, the initial treatment was traditional laser photocoagulation alone. In the drug group, the anti-VEGF drug was injected into vitreous once a month for three months. The initial treatment of the eyes in the combined group was laser combined with intravitreal injection of anti-VEGF drugs, or laser treatment within 1 week after anti-VEGF drug treatment. The follow-up time was more than 6 months, and best-corrected visual acuity (BCVA), ultra-wide-angle fundus photography, and fluorescein fundus angiography were performed during follow-up. The treatment efficiency, subretinal fluid (SRF), macular edema, BCVA and complications were compared among the three groups. ResultsAmong 60 patients (60 eyes), there were 55 males (55 eyes) and 5 females (5 eyes), with the mean age of 17.1±2.0 years. Among 60 eyes, there were 26 eyes in 2B stage, 23 eyes in 3A1 stage, and 11 eyes in 3A2 stage. Twenty patients (20 eyes) was in the laser group, combined group and drug group, respectively. After the initial treatment of all eyes in the drug group, the abnormal blood vessels did not regress significantly; the absorption and increase of SRF were 4 (20.0%, 4/20) and 5 (25.0%, 5/20) eyes, respectively. Supplementary laser therapy was given to 16 eyes, and vitrectomy (PPV) was given to 4 eyes. Among the 16 eyes treated by laser, 10 eyes were effective (50.0%, 10/20); vitreous hemorrhage, fibrous membrane hyperplasia, and complicated cataract occurred in 1, 1, and 2 eyes during the treatment, respectively, and PPV was given again in all eyes. Recurrent and persistent macular edema occurred in 4 and 1 eyes, respectively. Among the eyes in the combined group, treatment were effective in 11 eyes (55.0%, 11/20); 5, 2, and 2 eyes had SRF, fibrous membrane hyperplasia, and complicated cataract during the treatment, and PPV was given again; the edema was repeated and persisted in 1 eye, respectively. Among the affected eyes in the laser group, 15 eyes (75.0%, 15/20) were treated effectively; 2, 2, and 1 eyes developed a large number of vitreous hemorrhage, fibrous membrane hyperplasia, and complicated cataract during the treatment, and PPV was given again. ConclusionsAnti-VEGF drugs alone are ineffective in the treatment of Coats disease, and ablation of other abnormal blood vessels is needed. In the treatment of Coats disease, anti-VEGF drugs can not only promote the absorption of SRF, but also may lead to its increase, and the application should be cautious.
Macular pigment (MP) is composed of lutein, zeaxanthin, and meso-zeaxanthin, which accumulate mainly at the macula. MP has antioxidant function and can filtering blue wave. Measurement of MP is about its optical density, that is, macular pigment optical density (MPOD). This review summarizes the function and clinical use of MP and MPOD. Researches has show that MPOD is related to some ocular disease such as age-related macular degeneration, macular telangiectasia type 2, diabetic retinopathy, Stargardt disease et al. MPOD can be used in the judgment of clinical diagnosis, treatment effect. The specific mechanism of MP metabolism in the retina and in the pathogenesis of the disease, genotype specific nutritional therapy of xanthophyll, the establishment of a database combined with artificial intelligence and the rapid and convenient MP determination are all issues of great contention that need to be resolved.
ObjectiveTo observe the efficacy of intravitreal injection of ranibizumab (IVR) and combined treatment for severe Coats disease. MethodsNineteen Coats disease patients (24 eyes) were enrolled in this retrospective non-comparative interventional clinical study. The patients included 17 males and 2 females. The age was ranged from 1 to 42 years old, with an average of (13.05±6.78) years. The patients included 15 children (age ≤14 years old) and 4 adults (age ≥18 years old). There were 13 patients with 3a stage and 6 patients with 3b stage. The treatment methods including IVR only, IVR combined with cryotherapy, IVR combined with cryotherapy and sclerotomy to drain subretinal fluid, IVR combined with vitrectomy. Treatments were repeated if it was necessary at the first day, the first week and the first month after injection. The interval between treatments was ≥1 month. Eleven patients (57.9%) underwent one treatment, 3 patients (15.8%) underwent 2 treatments, 3 patients (15.8%) underwent 3 treatments, 2 patients (10.5%) underwent 4 treatments. The treatment frequency including 22 times of IVR only, 6 times of IVR combined with cryotherapy, 5 times of IVR combined with cryotherapy and sclerotomy to drain subretinal fluid, 1 time of IVR combined with vitrectomy. The follow-up period was ranged from 6 to 36 months, with an average of (19.11±7.05) months. Visual acuity, retinal reattachment and ocular adverse events were observed. ResultsThree children (15.8%) were failing to test the visual acuity. Visual acuity was improved in 2 patients (10.5%), stable in 13 patients (68.4%) and decreased in 1 patient (5.3%). Three patients (15.8%) achieved totally retinal reattachment after treatment, while 16 patients (84.2%) achieved partially retinal reattachment. One patient had vitreous hemorrhage. One patient had neovascular glaucoma. ConclusionIVR and combined treatment were effective for severe Coats disease.