“筑梦·铸人”专题

视网膜类器官衍生物的研究应用

An overview on applications of retinal organoid derivatives

:255-270
 
视网膜退行性疾病的种类繁多、患病人口基数大,该病特征为终末期严重的视网膜细胞丢失。视网膜类器官(retinal organoid,RO)可通过3D干细胞体外分化培养技术大量获取,并拥有完整的各亚型视网膜细胞和经典的视网膜分层结构。因此,RO可作为最佳的视网膜退行性疾病建模方法之一,以便于发现潜在致病机制。目前,RO衍生物已被广泛用于视网膜细胞替代治疗的动物实验和临床研究,具体的成效参差不齐,可能的影响因素包括移植细胞数量、移植时间窗、移植工具等。随着RO相关研究的快速发展,视网膜退行性疾病在分子和个体上的诊断和治疗将进一步完善。
Retinal degenerative diseases, characterized by severe retinal cell loss at the end stage, are of various kinds and haunt vast amounts of patients. Retinal organoid (RO) with complete retinal cell subtypes and classic retinal stratification structures can be obtained in large quantities through stem cells in vitro 3D differentiation and culture method. Therefore, RO can serve as one of the best ways for retinal degenerative disease modeling to facilitate the decipherment of underlying pathogenic mechanisms. At present, RO derivatives have been widely used in animal experiments and clinical studies of retinal cell replacement therapy with varying results possibly affected by cell quantity, time window, or tools in terms of transplantation. With the booming progress of RO-related research, the diagnosis and treatment on molecular and individual level for retinal degenerative diseases will be further improved.
“筑梦·铸人”专题

视网膜神经节细胞特异的报告基因干细胞系构建及其应用

Establishment and application of a retinal ganglion cell-specific reporter stem cell line

:245-254
 
目的:建立能驱动GFP在视网膜神经节细胞(retinal ganglion cell,RGC)中特异性表达的小鼠胚胎干细胞系。方法:通过同源重组的方式建立Brn3b-GFP敲入的小鼠胚胎干细胞系(Brn3b-GFP ESC),利用3D培养将其诱导成视网膜类器官检测GFP表达的细胞特异性,再用流式细胞分选富集GFP阳性RGC,采用玻璃体腔注射的方式将GFP阳性RGC移植到健康小鼠和NMDA损伤模型小鼠眼中探索该细胞的应用价值。结果:Brn3b-GFP ESC经3D视网膜诱导培养后在RGC中特异性表达GFP,将这些GFP阳性RGC移植到两种小鼠中2周后能在所有视网膜内观察到GFP阳性细胞存活,且均能观察到有供体RGC整合到宿主视网膜RGC层。结论:本研究建立了RGC特异的报告基因干细胞系Brn3b-GFP ESC,通过将该细胞系诱导成视网膜类器官进而获得的GFP阳性RGC移植后能够整合进宿主视网膜。该细胞系的建立将为青光眼及相关疾病提供重要的研究手段和工具。
Objective: This study was designed to establish a mouse embryonic stem cell line that can drive GFP expression specifically in retinal ganglion cells (RGCs). Methods: In this study, we established a Brn3b-GFP knock-in embryonic stem cell line (Brn3b-GFP ESC) by homologous recombination. By 3D culture, we induced these cells into retinal organoids to investigate the cell-specificity of GFP expression. GFP-positive RGCs were then enriched by flow cytometry and transplanted by intravitreal injection into the eyes of healthy mice and NMDA injury model mice to explore the feasibility of a potential clinical application. Results: GFP was specifically expressed in RGCs following induction of Brn3b-GFP ESCs into 3D retinal organoids. Two weeks after these GFP-positive RGCs were transplanted into the control and injured mice, GFP-positive cells were observed in all transplanted retinas, and donor RGCs were seen to integrate into the RGC layer of the host retina. Conclusion: This study has established a retinal ganglion cell-specific reporter stem cell line Brn3b-GFP ESC. The GFP-positive RGCs obtained by inducing the cell line into retinal organoids can be integrated into the host retina after transplantation. The establishment of such a cell line will provide an important research tool for glaucoma and related diseases.
病例报告

1例年轻患者视网膜分支静脉阻塞的10年随访

A 10-year follow-up report of retinal branch vein occlusion in a young patient

:978-984
 
视网膜静脉阻塞(retinal vein occlusion,RVO)是发生率仅次于糖尿病性视网膜病变的视网膜血管病。RVO后导致视网膜血管损伤进而引起血管闭塞,造成视网膜缺血从而促进异常视网膜新生血管(retinal neovascularization,RNV)的增生,晚期发生玻璃体积血、新生血管性青光眼等并发症,积极治疗可以稳定患者的眼部情况,避免并发症的发生。本文报告了1例患有高血压病的23岁年轻女性患者发生视网膜分支静脉阻塞并发新生血管增殖膜的病例,给予病变区视网膜激光光凝治疗,10年后随访发现RNV膜机化萎缩。
Retinal vein occlusion (RVO) is the second most common retinal vascular disease after diabetic retinopathy. Retinal vascular damage after RVO leads to venous occlusion, which further causes retinal ischemia and promotes abnormal retinal neovascularization (RNV). Later complications such as vitreous hemorrhage and neovascular glaucoma occur. Active treatment can stabilize the ocular condition of patients and avoid the occurrence of complications. This paper reports a case of a 23-year-old young female patient with hypertension who developed branch RVO complicated by neovascularization membrane. The lesion area was treated with laser photocoagulation. The RNV was found to be mechanized and atrophied after 10 years of follow-up.
论著

高度近视有晶状体眼后房型人工晶状体术后孔源性视网膜脱离的临床特征及预后分析

Clinical presentation and outcomes of rhegmatogenous retinal detachment in phakic eyes after posterior chamber phakic intraocular lens implantation for high-myopia

:111-116
 
目的:分析高度近视有晶状体眼后房型人工晶状体植入术后孔源性视网膜脱离的临床特征及预后。方法:回顾分析2012年4月至2021年6月中山眼科中心收治的9例(9只眼)行后房型人工晶状体植入术后孔源性视网膜脱离患者的临床特征、手术方式及疗效,随访(4.96±4.78)个月。结果:患者年龄(30.44±20.11)岁,屈光手术至发病时间(32.10±17.80)个月。4例(44.4%)马蹄形裂孔,1例(11.1%)萎缩性裂孔,4例(44.4%)巨大裂孔;9眼裂孔均位于赤道部前,除2眼(22.2%)为单个巨大裂孔,1眼(11.1%)单个马蹄孔,余6眼(66.7%)均有视网膜周边变性区存在;视网膜脱离范围(3.0±1.12)个象限,8例累及黄斑;增殖性玻璃体视网膜病变C级以上4眼。视网膜初始复位率为77.8%,最终视网膜复位率100%。末次随访最佳矫正视力优于术前(P<0.05)。随访期间,2例硅油填充眼发生并发性白内障,4眼发生术后早期高眼压。结论:有晶状体眼后房型人工晶状体植入术前存在的视网膜变性或术后玻璃体牵引的存在可能是孔源性视网膜脱离发生的危险因素。
Objective: To analyze the clinical presentation, surgical management, and outcomes of rhegmatogenous retinal detachment (RRD) in patients with high-myopia corrected by posterior chamber phakic (PCP) intraocular lens (IOL) implantation. Methods: Nine eyes of 9 patients in whom RRD developed after PCPIOL implantation from April 2012 to June 2021 in Zhongshan Ophthalmic Center were retrospectively studied. Mean follow-up after retinal detachment surgery was (4.96±4.78)months. Results: Mean patient age was (30.44±20.11) years old. RRD occurred (32.10±17.80) months after PCPIOL implantation. Four (44.4%) breaks were horseshoe tear, 1 (11.1%) was atrophic hole and 4 participants (44.4%) had a giant retinal tear. Nine cases had causative breaks located anterior to the equator while peripheral retina lattice degeneration was found in 6 eyes. RRD extended from 1 to 4 quadrants (3.0±1.12 quadrants) and 8 cases were macula-off retinal detachments. Four eyes’ proliferative vitreoretinopathy were more severe than level C. Initial reattachment rate was 77.80%. Final retinal reattachment was 100%. Final follow-up BCVA was significantly better than baseline (P<0.05). Furthermore, concurrent cataract occurred in 2 eyes in which silicone oil was used as tamponade. Ocular hypertension was detected in 4 eyes after surgery. Conclusion: The existed lattice degeneration and postoperative vitreous traction may be risk factors for RRD after PCPIOL implantation.
论著

右美托咪定与咪唑安定在麻醉监测管理下玻璃体视网膜手术中的对比

Comparison of dexmedetomidine versus midazolam for monitored anesthesia care in patients undergoing vitreoretinal surgery

:725-732
 
目的:在麻醉监测管理(monitored anesthesia care,MAC)中,通过与咪唑安定比较,观察右美托咪 定在玻璃体视网膜手术中应用的效果、安全性,探讨其应用可行性。方法:将择期玻璃体视网膜 手术患者40例随机双盲分入咪唑安定组(M组)和右美托咪定组(D组)。每组20例,两组患者均行球 后神经阻滞麻醉,连接脑电双频指数(bispectral index,BIS)监测仪监测并维持BIS值在70~90间, 观察和比较麻醉手术中及复苏期的平均动脉压(mean arterial pressure,MAP)、心率(heart rate, HR)、呼吸频率(respiratory rate,RR)、脉搏氧饱和度(oxygen saturation,SpO2)、Ramsay镇静评 分、疼痛数字评分法(Numerical Rating Scale,NRS疼痛评分)、手术医生和患者麻醉效果评分及不 良反应的差异。结果:与麻醉前比较,手术期D组用药后10 min内的心率、血压下降差异有统计学 意义(P<0.05),且用药后10 min内D组心率下降幅度较M组更大(P<0.05)。在手术期和复苏期,D组 的NRS疼痛评分均显著低于M组且差异有统计学意义(均P<0.001),而两组的Ramsay镇静评分差异 无统计学意义(P>0.05)。D组手术期患者的体动发生率和羟考酮使用率显著低于M组(均P<0.05)。 手术医生和患者的麻醉效果评分D组显著高于M组(均P<0.001)。结论:右美托咪定用于玻璃体视 网膜手术,较咪唑安定镇痛效果好且不良反应少,麻醉效果更好。

Objective: The aim of this study was to compare the efficacy and safety of dexmedetomidine versus midazolam for the monitored anesthesia care (MAC) management of patients undergoing vitreoretinal surgery. Methods: Forty patients undergoing selective vitreoretinal surgery were double-blind and randomly dividedinto midazolam group (group M) and dexmedetomidine group (group D), each group had 20 patients. Patients in both groups were anesthetized with posterior bulbous nerve block. Bispectral index (BIS) monitor was connected and the BIS value was maintained between 70 and 90. The mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), oxygen saturation (SpO2), Ramsay sedation score, numerical rating scale (NRS), surgeon’s and patient’s anesthesia effect score and adverse reactions were recorded during anesthesia and recovery period. Results: Compared with the data of pre-anesthesia, there were statistical differences of the decrease of HR and MAP in group D within the 10 minutes after medication (P<0.05), and the decrease of HR in group D was greater than that in group M (P<0.05). The NRS pain score in group D was significantly lower than that in group M with statistical significance (P<0.001) during the operation and resuscitation, while there was no significant difference in Ramsay sedation score between the two groups during the operation and resuscitation (P>0.05). In terms of adverse reactions to anesthesia, the incidence of spontaneous movement and oxycodone utilization in group D were significantly lower than those in group M (P<0.05). The anesthesia effect scores of surgeons and patients in group D were significantly higher than those in group M (all P<0.001). Conclusion: Dexmedetomidine has better analgesic effect and less adverse reactions than midazolam in vitreoretinal surgery.

论著

光学相干断层扫描血管成像观察玻璃体腔注射抗VEGF治疗视网膜分支静脉阻塞合并黄斑水肿的疗效

Optical coherence tomography angiography used to observe intravitreal injection of anti-VEGF on branch retina vein occlusion combined with macular edema

:28-32
 
目的:以光学相干断层扫描血管成像(optical coherence tomography angiography,OCTA)观察视网膜分支静脉阻塞(branch retinal vein occlusion,BRVO)抗血管内皮生长因子(vascular endothelial growth factor,VEGF)治疗前后的变化。方法:回顾性收集从2017年1月至2018年1 2月在汕头国际眼科中心的确诊为BRVO合并黄斑水肿的患者共3 1例3 2眼。患眼行玻璃体腔注射抗VEGF药物治疗,记录治疗前和治疗后1个月的最佳矫正视力(best corrected visual acuity,BCVA),OCTA检查视网膜黄斑中心凹厚度(foveal macular thickness,FMT)、黄斑区血流密度。比较治疗前后各指标的变化。结果:治疗后BCVA较治疗前显著提高,差异有统计学意义(P<0.001);FMT[(242.13±86.02) μm]较治疗前[(521.44±190.27) μm]明显下降,差异有统计学 意义(P<0.001);中心凹浅层血流密度[(18.44±4.98)%]及中心凹旁浅层血流密度[(44.83±3.19)%]均较治疗前[(25.46±9.21)%,(46.06±5.25)%]相比明显下降,差异有统计学意义(P <0.001)。结论:玻璃体腔注射抗VEGF治疗BRVO合并黄斑水肿效果显著;OCTA能有效评价抗VEGF治疗BRVO合并黄斑水肿的临床疗效。
Objective: To evaluate the efficacy in patients with macular edema due to branch retinal vein occlusion (BRVO) treated with intravitreal anti-VEGF drug. Methods: In this retrospective study, 32 eyes of 31 patients with BRVO combined with macular edema at Joint Shantou international eye center of Shantou University and TheChinese University of Hong Kong during January 2017 to December 2018 were enrolled in this study. All the affected eyes received intravitreal anti-VEGF drug injections. BCVA (best corrective visual acuity) and optical coherence tomography angiography (OCTA) were performed before and one month after intravitreal anti-VEGF drug injections. Foveal macular thickness (FMT), macular blood flow density was measured in all eyes and compared. Results: The BCVA before therapy was (0.77±0.46) LogMAR and increased to (0.46±0.30) LogMAR in one month after therapy, which showed a statistical difference (P<0.001). The FMT, foveal superficial vascular plexus flow density and para foveal superficial vascular plexus flow density before therapy were (521.44±190.27) μm, (21.85±6.17)% and (46.29±2.70)%, respectively. The FMT, foveal superficial vascular plexus flow density and para foveal superficial vascular plexus flow density decreased to (242.13±86.02) μm, (18.40±5.18)% and (44.75±3.40)%, respectively. There was significant statistical difference for them (P<0.001). Conclusion: Intravitreal injection of anti-VEGF is effective in the treatment of BRVO combined with macular edema. OCTA can effectively evaluate the clinical efficacy of anti-VEGF in the treatment of BRVO combined with macular edema.
其他期刊
  • 眼科学报

    主管:中华人民共和国教育部
    主办:中山大学
    承办:中山大学中山眼科中心
    主编:林浩添
    主管:中华人民共和国教育部
    主办:中山大学
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  • Eye Science

    主管:中华人民共和国教育部
    主办:中山大学
    承办:中山大学中山眼科中心
    主编:林浩添
    主管:中华人民共和国教育部
    主办:中山大学
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