Age-related macular degeneration (AMD), particularly the wet form characterized by choroidal neovascularization, is a leading cause of vision loss. Dysregulation of regulatory T cells (Tregs), key modulators of inflammatory responses, may contribute to wet AMD pathogenesis. This study explored the involvement of Tregs and the Rac1 signaling pathway in modulating Treg-derived cytokine expression and their role in choroidal neovascularization during wet AMD progression. Peripheral blood samples from healthy controls, dry AMD patients, and wet AMD patients were collected. An in vitro transmembrane co-culture system of Tregs and human choroidal endothelial cells (HCECs) was employed to investigate the impact of Tregs (with or without Rac1 silencing) on the angiogenic phenotype of HCECs. A mouse model of AMD was established to evaluate the effects of a Rac1 inhibitor and IL-10/TGF-β neutralization on Tregs and choroidal neovascularization. An increased Treg percentage in the CD4+ T lymphocyte population was found in the peripheral blood samples of wet AMD patients. Tregs from wet AMD patients showed an increased expression of Rac1 and an elevated production of IL-10 and TGF-β1. Rac1 silencing suppressed Treg stability and differentiation, and impaired the pro-angiogenic effect of Tregs on HCECs. In the animal model of AMD, the administration of a Rac1 inhibitor or neutralizing antibodies against IL-10/TGF-β1 reduced Treg abundance and attenuated choroidal neovascularization. Rac1 upregulation in Tregs promoted IL-10 and TGF-β1 production to mediate choroidal neovascularization in wet AMD. Targeting Rac1 and Treg-derived IL-10/TGF-β1 production in Tregs may serve as a strategy to ameliorate AMD progression.
Glaucoma is a degenerative disease characterized by retinal ganglion cell (RGC) death and visual impairment caused by elevated intraocular pressure (IOP). Elevated IOP can activate microglia, which participate in ganglion cell injury. Based on the study of caveolin-1 (Cav-1) in glaucoma, we aimed to explore the effect and mechanism of Cav-1 on RGC apoptosis in mice with acute ocular hypertension (AOH). AOH mice were established, and Cav-1 was intravitreally injected. Retinal microglia and RGCs were isolated from neonatal mice. TUNEL staining, hematoxylin-eosin staining, immunohistochemistry, flow cytometry, PCR and western blotting were used to observe the effect of Cav-1 on RGCs and mouse retinas. The thickness of the whole retina and the inner retinal sublayer decreased significantly, retinal cell apoptosis increased after AOH injury, and Cav-1 treatment reversed the effect of AOH injury. In addition, Cav-1 treatment promoted the conversion of proinflammatory M1 microglia to anti-inflammatory M2 microglia. Microglia and RGCs were isolated from neonatal mice. Cav-1 protects RGCs from OGD/R-induced injury by changing the polarization status of retinal microglia in vitro. Further studies revealed that Cav-1 activated the Akt/PTEN signaling pathway and inhibited TLR4. Our study provides evidence that Cav-1 may be a promising therapeutic target for glaucoma.
目的 探索布鲁姆目标教学法联合案例教学法在眼科大课教学中的应用价值.方法 选择 2019 年 2 月至 2020年 6 月由云南大学附属医院承担眼科大课教学的昆明医科大学本科生为研究对象,其中 68 名学生采用融入布鲁姆目标教学法和案例教学法的教学方案(观察组),88 名学生采用传统教学方案(对照组),教学完成后两组学生均采用相同的笔试及问卷调查.结果 观察组理论考试成绩优于对照组,差异有统计学意义(P<0.05);观察组学生对调动兴趣、深化理解和提高临床思维能力 3 个方面的满意率优于对照组学生,差异有统计学意义(P<0.05).结论 融入布鲁姆目标教学法和案例教学法的教学方案有助于提高学生理论考试成绩,有助于学生提高学习兴趣,更好地深入理解学习内容,提高临床思维能力.
Retinal ischemic disease is a major type of retinal diseases causing vision loss. Identifying the molecular mechanisms mediating the retinal ischemia-reperfusion (RIR) is the key to targeted intervention. In this study, we performed RNA-seq analysis of the retinal tissues of a retinal ischemia-reperfusion model of Sprague-Dawley (SD) rats, followed by differential gene expression analysis, gene ontology (GO) enrichment analysis, and protein-protein interaction (PPI) analysis. After studying we found that: The major biological processes affected after RIR was the regulation of vascular development. PPI analysis unveiled a regulatory module in which Platelet Derived Growth Factor Receptor Beta (PDGFRB) was upregulated. In the RIR cell model of human retinal microvascular endothelial cells (HRCEC) induced by oxygen-glucose deprivation/reperfusion (OGD/R), silencing PDGFRB at least partially rescued the detrimental effect on cell proliferation and in vitro angiogenic ability. In the rat model of RIR, the administration of PDGFR inhibitor alleviated the damages in the retinal microvascular system. Besides, we further demonstrated the protective effect of procyanidin against RIR induced damages in both the cell and animal model by dampening the overexpression of PDGFRB. Together, our data indicate that the upregulation of PDGFRB contributes to RIR-induced damages in retinal microvascular system, which provides a targetable strategy for therapeutic intervention.
Age-related macular degeneration(ARMD)is a main cause of irreversible visual impairment in the elderly. The major pathological features are drusen formation, macular pigment disorder, geographic atrophy and abnormal neovascularization. Retinal pigment epithelium(RPE)function is impaired in ARMD. Endoplasmic reticulum(ER)is an organelle in eukaryotes responsible for protein synthesis, modification, integration and quality control. ER also participates in the maintenance of calcium homeostasis and lipid biosynthesis. Stimuli from the external and internal environment may trigger ER stress and therefore activate the intracellular signal transduction pathway-the unfolded protein response(UPR), to restore cell homeostasis. However, prolonged ER stress may lead to apoptosis. The pathogenesis of ARMD has not been fully elucidated, nevertheless, compelling evidence demonstrates that ER stress is involved. In this article, we summarize recent advances in UPR pathways, as well as the role of ER stress in the physiological function of RPE and in the pathogenesis of ARMD.
Objective:To observe the clinical evolution process and imaging characteristics of choroidal lesions in different subtypes of serpiginous choroiditis (SC), and to explore the clinical significance of subtype classification.Methods:A retrospective, uncontrolled and observational study. A total of 45 eyes of 25 SC patients diagnosed in Yunnan Eye Hospital from May 2009 to September 2021 were included in the study. According to the initial location of the lesion and fundus images, including fundus color photography, fundus fluorescein angiography (FFA), optical coherence tomography (OCT) and other examination results. SC was divided into peripapillary serpiginous choroiditis, macular serpiginous choroiditis and ampiginous choroiditis. According to the shape of the lesions at the first diagnosis, it can be divided into new lesions with only infiltrating edema, old lesions with only atrophy and recurrent lesions with coexistence of edema and atrophy. the imaging features, development and complications of different subtypes of ocular lesion were observed.Results:Among the 45 eyes of 25 cases, 15 cases were male and 10 cases were female, 20 cases of binocular and 5 cases of monocular, age was 42.3±5.7 years old. There were 21 eyes with active lesions, of which 5 eyes were new lesions and 16 eyes with recurrent lesions; 24 eyes were old lesions. Concurrent optic disc edema occurred in 3 eyes; mild vitreitis occurred in 5 eyes; retinal occurred vasculitis in 3 eyes; choroidal neovascularization occurred in 3 eyes. Among the 16 cases (64%, 16/25) of the peripapillary serpiginous choroiditis, 2 cases (2 eyes) were monocular, and 14 cases (28 eyes) were binocular. Active lesions were found in 16 eyes, of which patients with binocular lesions only one had active lesions. The choroidal lesions that were close to the optic disc or around the optic disc, expanded outwards centrifugally with the prolongation of the disease course, and can progress to the macula. The edge of the lesion was tortuous, with a geographic-like, amoeboid-like and finger-like, polypoid or propeller-like shape. Active lesions in FFA showed weak fluorescence in the early stage and strong fluorescence in the late stage; the old lesions showed weak fluorescence in the early stage and mottled fluorescence in the late stage, and mostly strong fluorescence on the edge. OCT showed thickening of active lesions and thinning of old lesions. Among the 4 cases (16.0%, 4/25) of macular type, 2 cases (2 monocular eyes) had active lesions; 2 cases (4 eyes) had lesion in both eyes, among them, 1 case (2 eyes) had old lesion, and the other case had alternate active lesions. The initial lesions were all located in the off-center of the macula, and most of them were disk-shaped and progressing centrifugally to the periphery. The FFA and OCT imaging findings of the lesions were similar to those of the peridisc type. Among the 5 cases (20.0%, 5/25) of ampiginous choroiditis, 1 case (1 eye) was monocular and 4 cases (8 eyes) were binocular. These lesions were multiple old lesions of varying sizes, gray-white with pigmentation, with clear borders in the posterior pole. Among them 4 eyes have new active lesions appeared near the old lesions. The old lesions showed weak fluorescence with clear borders, and the fluorescein leakage at the late edge formed a strong fluorescence ring; the active lesions showed weak fluorescent spots with blurred edges, and the fluorescence was slightly enhanced in the late stage. In old lesions, atrophy of the photoreceptor layer, RPE and choroid can be seen, and RPE hyperplasia in some areas.Conclusions:SC subtype is a classification of the location of the first lesion, but the characteristics of the repeated attack of this disease can lead to the annihilation of each subtype due to the continuous expansion of the lesion. The phenomenon that the fundus active lesions only occur in one eye that can explain the clinical manifestations of asymmetric morphology of binocular lesions. The characteristics of binocular subtype warn that the predilection site of the healthy eye should be paid attention to.
目的 探索磁性微珠前房注射诱导高眼压模型的可行性及特点,OCT在模型评估中的作用.方法 将C57BL/6小鼠分为正常组、对照组与实验组.实验组前房内注射磁性微珠诱导高眼压,对照组前房内注射等量生理盐水,正常组不做任何处理.术前及术后第1天开始隔天检测眼压波动;建模3周后行荧光金逆行标记,建模4周后使用OCT检测两组小鼠视盘旁神经纤维厚度,并行视网膜行铺片计数各组RGCs数量.结果 小鼠前房内注射磁性荧光微珠后,微珠可均匀分布于房角处堵塞房角.实验组小鼠眼压自注射术后1 d开始升高,平均眼压为(19.37±4.38)mmHg,3周开始眼压下降;荧光金逆行标记RGCs,建立微珠诱导小鼠高眼压模型后4周,行OCT检测RNFL厚度.实验组RNFL厚度为(27.67±6.15)μm,较对照组明显变薄,两组比较差异有统计学意义(P=0.0082).检测OCT后收集眼球计数RGCs,实验组RGCs为(203.83±26.35)个,与对照组比较明显减少,差异有统计学意义(P=0.0094).结论 小鼠前房注射磁性微珠可以诱导持续稳定的眼压升高并引起明显RGC数量减少,可通过OCT无创、快速、重复的检测神经纤维层厚度发现RGC损伤.
Drug‐induced liver injury (DILI) can lead to acute liver failure, a lethal condition which may require liver transplantation. Hepatotoxicity associated with nonsteroidal anti‐inflammatory drugs (NSAIDs) accounts for ~ 10% of all DILI. In the current study, we determined whether indomethacin, one of the most commonly used NSAIDS, induced apoptosis in hepatocytes and investigated the underlying mechanism. Meanwhile, we investigated the protective effect of S‐allyl‐L‐cysteine (SAC), an active garlic derivative, on indomethacin‐induced hepatocyte apoptosis, and its implication on endoplasmic reticulum (ER) stress. We found that indomethacin triggered ER stress, as indicated by the elevated expression of phosphorylated eukaryotic translation initiation factor 2α (eIF2α), C/EBP homologous protein (CHOP) and spliced XBP1 in a rat liver BRL‐3A cell line. Following indomethacin treatment, caspase 3 activation and hepatocyte apoptosis were also observed. Inhibition of ER stress by chemical chaperone 4‐phenyl butyric acid alleviated cell apoptosis caused by indomethacin, indicating that ER stress is involved in indomethacin‐induced hepatocyte apoptosis. Moreover, SAC abated indomethacin‐induced eIF2α phosphorylation, inhibited CHOP upregulation and its nuclear translocation, abrogated the activation of caspase 3 and finally, protected hepatocytes from apoptosis. In conclusion, SAC protects indomethacin‐induced hepatocyte apoptosis through mitigating ER stress and may be suitable for development into a potential new therapeutic agent for the treatment of DILI.
Diabetic retinopathy (DRP) is a retinal disease caused by diabetes mellitus, which is categorized by microvascular lesions present in the retina such as vascular leakage, vascular proliferation, and retinal ischemia. The plan of the present study was to the synthesis of Cyperus rotundus‐loaded zinc oxide nanoparticles (CR‐ZnONPs) which was confirmed by the various characterization methods such as UV‐vis spectroscopy, energy dispersive X‐ray analysis, Fourier transform infrared, scanning electron microscope, and X‐ray diffraction. Also, the effect of CR‐ZnONPs on DRP‐induced rats was determined by food intake, fasting blood glucose (FBG), HbA1c, insulin, retina thickness, inner nuclear layer (INL), outer nuclear layer (ONL) thickness, lipid peroxidation (LPO), catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). Furthermore, the status of oxidative stress marker genes (heme oxygenase‐1 [HO‐1] and nuclear factor erythroid 2‐related factor‐2 [Nrf2]) and inflammatory marker (procaspase‐1, cleaved‐caspase‐1, interleukin‐1β [IL‐1β], IL‐18, and ASC) expressions were examined by using real‐time polymerase chain reaction and Western blot analysis techniques. We noted that the synthesized CR‐ZnONPs have a crystalline structure, spherical shape, and present various functional groups. The administration of streptozotocin (STZ)‐induced DRP rats were increased in the levels of HbA1c, FBG, food intake, LPO, and reduced levels of insulin, SOD, GPx, and CAT. In addition, the gene and protein expression showed the downregulation of HO‐1 and Nrf2 and upregulation of procaspase‐1, IL‐1β, cleaved‐caspase‐1, IL‐18, and ASC in diabetic rats. Moreover, further histopathological analysis of retinal tissues again confirmed the results of biochemical parameters. In contrast, the DRP rats treated with CR‐ZnONPs significantly brought down all the parameters to normal, which indicated that the CR‐ZnONPs have better antidiabetic and anti‐inflammatory properties.
目的 建立急性高眼压(acute ocular hypertension,AOH)小鼠模型,探索视网膜中窖蛋白(Caveolin,Cav)-1表达变化,明确其是否参与青光眼视网膜损伤的病理生理过程.方法 C57小鼠75只,60只纳入实验组,15只纳入对照组.对照组不做任何处理,实验组随机选取一眼建立AOH小鼠模型.分别于造模后1d、2d、3d、7d取眼球或视网膜通过荧光定量PCR(Q-PCR)、Western blot、免疫荧光检测Cav-1 mRNA和蛋白表达变化,并与对照组比较.结果 Q-PCR检测结果显示,实验组小鼠造模后1 d、2 d、3 d、7 d时视网膜中Cav-1 mRNA表达均升高,与对照组比较差异均有统计学意义(均为P<0.05),其中造模后2 d表达最高.Western blot检测结果显示,Cav-1蛋白在造模后2 d、3 d、7 d的实验组小鼠视网膜中表达均升高,与对照组比较差异均有统计学意义(均为P<0.05),其中造模后3d表达最高.免疫荧光检测结果显示,Cav-1在造模后1d、2d、3d、7d均可检测到高荧光表达.结论 Cav-1参与了AOH的病理过程,并且其表达变化在早期较明显.
Abstract Increasing evidence has shown that microRNAs (miRNAs) play an important role in the pathogenesis of diabetic retinopathy (DR). However, the role and mechanism of miRNA in regulating high glucose (HG)-induced ARPE-19 cell injury are still not well understood. The present study aimed to investigate the effects of miR-200a-3p on DR progression and reveal the underlying mechanisms of their effects. In the present study, we observed that miR-200a-3p was significantly decreased, while transforming growth factor-β2 (TGF-β2) expression was up-regulated in ARPE-19 cells treated with HG and retina tissues of DR rats. Subsequently, overexpression of miR-200a-3p significantly promoted cell proliferation, reduced apoptosis, as well as inhibited the levels of inflammatory cytokines secreted, matrix metalloprotease 2/9 (MMP2/9), and vascular endothelial growth factor (VEGF) in HG-injured ARPE-19 cells. Moreover, miR-200a-3p was proved to target TGF-β2 mRNA by binding to its 3′ untranslated region (3′UTR) using a luciferase reporter assay. Mechanistically, overexpression of miR-200a-3p reduced HG-induced ARPE-19 cell injury and reduced inflammatory cytokines secreted, as well as down-regulated the expression of VEGF via inactivation of the TGF-β2/Smad pathway in vitro. In vivo experiments, up-regulation of miR-200a-3p ameliorated retinal neovascularization and inflammation of DR rats. In conclusion, our findings demonstrated that miR-200a-3p-elevated prevented DR progression by blocking the TGF-β2/Smad pathway, providing a new therapeutic biomarker for DR treatment in the clinic.
Objective:To observe the clinical and imaging characteristics of acute idiopathic macular degeneration (AIM).Methods:A retrospective clinical study. From March 2016 to January 2018, 5 eyes (5 AIM patients) in The Second People's Hospital of Yunnan Province were included in the study. Among them, there were 4 males (4 eyes) and 1 female (1 eye); all patients were monocular with the average age of 34.2 years. The course of illness from onset of symptoms to treatment was 4-22 days. All affected eyes were examined by BCVA, fundus color photography, OCT, FAF, and FFA. Among 5 eyes, 1 eye with optic disc vasculitis was given oral glucocorticoid treatment; 4 eyes were not interfered after the diagnosis.Results:The follow-up time was 6 months. During follow-up, BCVA, fundus color photography, and OCT examination were performed. The results were all a sudden decrease in monocular vision, accompanied by visual distortion or central dark spots. At the first visit, the BCVA was 0.1, 0.2, 0.2, 0.05, and 0.5; at the last follow-up, the BCVA of the affected eye was 0.8, 0.6, 0.5, 0.5, and 1.0, respectively. Fundus color photography showed that at the first diagnosis, all the affected eyes showed irregular round yellow-white lesions in the macular area, including 1 eye with small patches of hemorrhage and 1 eye with pseudopyous changes in the macular area. Two to three weeks after the initial diagnosis, the yellowish-white lesions and bleeding in the macular area were basically absorbed. The center of the lesion showed weak pseudopod-like fluorescence, and the surrounding area was surrounded by strong fluorescence in FAF examination. The irregular and strong fluorescence in the early macular area and accumulation of late fluorescein in FFA examination. One eye was receivied glucocorticoid therapy. The upper layer of the retinal nerve in the macular area was detached, and the inferior space showed focal strong reflective material in 3 eyes in OCT examination. At the first diagnosis, the retinal neuroepithelial layer was detached, the top of the RPE layer was irregular with strong reflective material, and the structure of the ellipsoid zone and the chimera zone was unclear; as the course of the disease prolonged, the outer retinal structure recovered.Conclusions:AIM is characterized by inflammatory exudative changes in the outer layer of the retina in the macular area; FFA is characterized by strong subretinal disc-like fluorescence or multifocal weak fluorescence in the macular area; OCT mainly manifests as neuroepithelial detachment and changes in the outer retina and RPE, The structure can be restored by itself.
目的 对早产儿视网膜出血进行统计,分析探讨早产儿视网膜出血的危险因素及临床特点.方法 选取2013年1月—2016年12月在我院进行眼底病筛查的早产儿1142例进行回顾性分析,患儿均在散瞳后实施眼底检查,观察视网膜出血情况,评估影响视网膜出血的相关因素.结果 1142例早产儿中,视网膜出血有112例,占9.8%,视网膜出血程度分级Ⅰ、Ⅱ、Ⅲ、IV级分别有42例、47例、23例、0例,分娩方式是引起视网膜出血的主要危险因素,经阴道分娩的早产儿发生视网膜出血的几率较剖宫产高,差异具有统计学意义(P<0.05),是否使用机械通气及助产与视网膜出血也密切相关.结论 分娩方式及机械通气是导致早产儿视网膜出血的重要原因,经阴道分娩的难产患儿是高危人群.
Objective To investigate the clinical features of perforating injury of eyeball by metallic foreign body,together with the discussion of the primary treatment,the vitreoretinal surgery time,the surgical technique and the therapeutic evaluation.Method Medical records of 15 cases ( 16 eyes) of ocular perforating injury by metallic foreign body were retrospectively analyzed.Results The follow-up was from 2 week to 2 years.Two cases that had not undergone surgery were resulted in a corrected visual acuity of 0.8.Fourteen patients gained visual acuity increase after operation.The retina reattached in 12 eyes after the first pars plana vitrectomy (PPV),and in 2 eyes after the secondary PPV.Two foreign bodies on eyeball wall and 3 foreign bodies in orbit were extracted.There was no complication observed in 11 cases with foreign bodies persist in orbit.Conclusion For perforating injury with mild vitreous hemorrhage,medicine treatment was used if the wound can be self-closed.For perforating injury with serious vitreous hemorrhage,it is proper to perform vitreoretinal surgery between 7 - 14 days later.For perforating injury with retinal detachment or with infection sign,it is proper to carry out vitreoretinal surgery as early as possible.It is a welladvised choice to pack the postern scleral wound by gelatin sponge.Inert gas or silicone oil tamponade were used according to the condition of vitreous body and retina.
<正>第三代重硅油Oxane HD作为近年来出现的新型玻璃体填充物,用于治疗复杂性视网膜脱离,我院于2008年12月至2010年12月间运用Oxane HD治疗陈旧性视网膜脱离病例23例,并总结报道如下。1资料与方法1.1一般资料回顾性分析2008年12月至2010年12月我院眼科收治的陈旧性视网膜脱离病例23例(24眼),诊断主要依据患者主诉和病史,以及眼底检查发现广泛或局限性视网膜下
Objective To evaluate the clinical application of BacT/ALERT 3D automated blood culture system in traumatic endophthalmitis.Methods A total of 113 vitreous specimens of traumatic endophthalmitis were collected by BacT/ALERT PF pediatric blood culture bottle,detected by BacT/ALERT 3D automated blood culture system and analysed by Vitek-2 compact.We evaluated the positive rate,time to show positive,the types of microorganisms.Results In a total of 113 cultured vitreous specimens,81 cases were positive.Positive rate was 71.7%.Grampositive microorganisms accounted for 62.9% of the positive culture results.Gramnegative microorganisms accounted for 34.6% and fungi accounted for 2.5%.The shortest time to show positive was 4h.Conclusion The automated blood culture system has been widely used in blood and body fluid culture.The application of the automated blood culture for endophthalmitis can raise the positive detection rate,reduce the detection time to show positive and increase the types of microorganisms detected.
目的:探讨现代玻璃体切除手术联合眼内充填重硅油治疗严重眼外伤的疗效。方法:对2009/2010年我院收治的21例严重眼外伤患者应用现代玻璃体切除联合重硅油填充手术治疗,一期清创缝合联合玻璃体手术者7例,一期清创缝合二期行玻璃体手术者14例。术后随诊3~12(平均7.5)mo,观察术后效果。结果:术后17例眼球完全保留,4例眼球萎缩。10例视力较术前不同程度提高。结论:应用现代玻璃体切除重硅油填充术治疗严重眼外伤,不仅能保留眼球完整,也会提高部分视力。
目的:评价泪囊囊肿手术的疗效。方法:采用泪囊囊肿切除合并改良式泪囊鼻腔吻合术治疗泪囊囊肿患者33例(37眼)。结果:33例患者,治愈32例36只眼,治愈率97.29%。结论:应用泪囊囊肿切除合并改良泪囊鼻腔吻合术治疗泪囊囊肿疗效良好,安全可行,并发症少。