复杂性眼外伤患者玻璃体切割围手术期护理体会

目的:玻璃体切割术是眼科手术中比较复杂精细显手术,主要应用于治疗眼外伤导致的玻璃体出血,玻璃体浑浊,复杂性视网膜脱离以及增殖性玻璃体视网膜病变。本文主要探讨玻璃体切割术治疗复杂性眼外伤患者的围手术期护理的临床效应。方法:总结作者所在科室多年来护理眼外伤患者的临床经验,对2013年3月至2013年7月入院的75例(75只眼)复杂性眼外伤患者进行悉心的术前心理护理,完善的用药指导,充分的术前准备,术后特殊卧位的指导,预防并发症的护理及出院指导。结果:术后视力提高57例(76.0%),视力不变13(17.3%)例,视力下降5例(6.7%),28例眼内异物患者均经手术顺利取出异物。相关手术并发症经医护人员的对症治疗后均得到有效控制。患者术后满意度达98%以上,医生满意度达100%。结论:复杂性眼外伤患者玻璃体切割手术围手术期进行全方位的护理服务,对促进病人康复起到至关重要的作用。     

降纤酶治疗视网膜静脉阻塞疗效的观察

视网膜静脉阻塞(RVO)是常见的视网膜血管病,病因复杂,故治疗本病较困难,且其病程缓慢,冗长,晚期常见有黄斑囊样水种和新生血管形成,导致患者视功能明显减退,甚至失明。我们于1999年2月始用降纤酶配合其他一些辅助药物治疗30例RVO患者并于随访,现将结果报告如下。1 临床资料1.1 一般情况:30例(30眼),男18例,女12例,其中右眼17例,左眼13例。年龄19～75岁,平均52岁,40岁以上23例,40岁以下7例。均为单眼发病,     

玻璃体视网膜手术治疗先天性视网膜劈裂及其并发症的临床疗效

目的:评价玻璃体视网膜手术治疗先天性视网膜劈裂及其并发症的临床疗效。方法:选择2009年1月-2012年1月于我院进行玻璃体视网膜手术的先天性视网膜劈裂患者30例(42只眼),患者均接受了闭合式睫状体经扁平部三切口入路保留晶状体的玻璃体切割手术,并分析其术前及术后情况。结果:先天性视网膜劈裂患者中发生孔源性视网膜脱离19眼,牵拉性视网膜脱离8眼,玻璃体积血10眼,同时伴有视网膜脱离和玻璃体积血有5眼;在末次随访时视力提高者有36只眼,占85.71%,无提高者有6只眼,占14.29%;术前平均视力为(0.15±0.09),末次随访时平均视力提高至(0.31±0.16),两者平均视力差异具有统计学意义(t=5.649,P0.001);42只眼视网膜解剖结构复位良好,视网膜平伏;OCT检查结果显示,末次随访时黄斑劈裂平均面积(0.22±0.18)mm2,与术前黄斑劈裂平均面积(1.07±0.52)mm2比较,差异有统计学意义(t=10.011,P0.001),黄斑微囊样改变有改善;随访期间5只眼出现并发症,占11.90%,其中2眼术后发生PVR且伴牵拉性视网膜脱离,2只眼发生白内障,1只眼出现玻璃体积血,术后视网膜解剖均复位良好。结论:玻璃体视网膜手术可以帮助患者进行视网膜解剖复位及提高其先天性视网膜劈裂患者视功能,具有良好的临床疗效。     

24 例眼外伤继发性青光眼的临床分析

目的:分析眼外伤继发青光眼的临床特点、病因及治疗方法,为临床治疗提供参考。方法:回顾性分析24例(24只眼)眼外伤继发青光眼患者的临床资料,分析诱发青光眼的原因、临床分型,根据具体情况选择治疗方法。结果:眼外伤诱发青光眼的原因为眼内积血11例,晶状体损伤7例,前房角挫伤4例,外伤性虹睫炎2例;单纯药物治疗4例,前房穿刺或冲洗4例,小梁切除联合丝裂霉素术10例,玻璃体切除术2例,滤过手术1例,激光周边虹膜切除术5例。治疗后随访6~12个月,眼压恢复正常率87.50%;视力下降或丧失8.33%;术中1例眼出血,1例术后晶体状浑浊加重,1例视网膜脱离。结论:眼外伤继发青光眼的临床表现复杂,治疗难度大,临床应根据患者的具体情况选择治疗措施。     

帕金森病及运动障碍疾病门诊震颤患者的病因及临床表现分析

目的:总结帕金森病及运动障碍疾病门诊震颤患者的病因及临床表现,以提高门诊震颤患者的诊断率,降低误诊率,为门诊震颤诊断提供临床经验。方法:连续收集西京医院神经内科帕金森病及运动障碍疾病门诊自2015年5月至2016年7月收治的震颤患者进行横断面研究。采用SPSS19.0软件进行统计分析。结果:共纳入400例震颤患者,男性173例(43.3%),女性227例(56.8%),男女之比1:1.3,平均发病年龄54.0岁。40岁以下特发性震颤(ET)最多,41-60岁为帕金森病(PD),60岁以上帕金森病最多。震颤按临床表现形式分为静止性震颤85例(21.3%),动作性震颤137例(34.3%),混合性震颤178例(44.5%)。震颤按病因分类,占比例前三位的分别是:帕金森病(46.3%),特发性震颤(28.5%),心因性震颤(5.8%)。心因性震颤急性起病率及合并焦虑抑郁率最高,而PT画螺旋圈及书写阳性率明显低于其他病因组。结论:门诊震颤患者混合性震颤形式较多见,最常见病因为帕金森病、特发性震颤及心因性震颤;心因性震颤较其他病因所致震颤相比,急性起病率、合并焦虑抑郁率高,而画螺旋圈及书写阳性率低。震颤诊断应先明确震颤的临床特点,然后分析病因以确定诊断及治疗。     

玻璃体腔注药联合微创玻璃体切除治疗糖尿病视网膜病变的临床疗效研究

目的:探讨玻璃体腔注药联合微创玻璃体切除治疗糖尿病视网膜病变的临床疗效。方法:选择2014年1月至2016年1月在我院确诊并治疗的增生性糖尿病视网膜病变患者80例,共83只患眼,随机分为A、B两组。A组共42例患眼,接受25 G玻璃体微创手术;B组共41例患眼,在A组治疗的基础上给予玻璃体腔注射康柏西普。比较两组患者的手术情况、治疗前后最佳视力的矫正(Best-corrected visual acuity,BCVA)情况、视网膜厚度以及术后1个月不良反应的发生情况。结果:B组患者的手术时间较A组显著缩短(P0.05),且术中使用电凝的患眼、术中出血以及术中发生医源性裂隙的患眼比例显著低于A组(P0.05),新生血管消失的患眼比例显著高于A组(P0.05)。B组患者术后1个月和3个月的BVCA显著高于A组(P0.05),且术后视网膜的厚度显著薄于A组(P0.05),术后发生玻璃体积血和前方出血的患眼比例显著低于A组(P0.05)。结论:玻璃体腔注射康柏西普联合25G玻璃体微创切除术治疗增生性糖尿病视网膜病变的临床疗效显著,有利于患者术后视力以及视网膜恢复。     

2009例藏族白内障患者的病因构成及相关因素分析

目的:分析2009例藏族白内障手术患者的病因构成及相关因素。方法:收集2013年10月至2014年10月西藏自治区藏医院眼科2009例藏族白内障手术患者病例资料,按病因、年龄、性别、白内障类型、人工晶状体屈光度、文化程度、经济水平进行分类,运用统计学方法分析西藏地区藏族白内障患者发病特点。结果:2009例藏族白内障手术患者中,年龄相关性白内障1885眼(93.83%),核性白内障1197例(59.58%)。年龄2-89岁,平均年龄62.53岁,男1012眼(50.37%),女997眼(49.63%)。50-59岁年龄组的核性白内障患者比例明显高于40-49岁年龄组(P0.01;80-89岁年龄组的核性白内障患者比例高于70-79岁年龄组(P0.05)。根究Emery分级,50-59岁年龄组Ⅳ级白内障患者比例明显高于40-49岁年龄组(P0.01);80-89岁年龄组Ⅳ级白内障患者比例明显高于70-79岁年龄组(P0.05)。术前裸眼视力为0.02及0.02以下1688例(84.02%)。高度近视患者13例(0.65%),远视患者406例(20.21%)。农牧区患者1310例(65.21%),明显多于其他行业患者。结论:年龄相关性白内障仍是西藏地区藏族白内障患者的主要病因,以核性白内障为主要发病类型。随年龄增长,核性白内障患者越来越多,核硬度分级越来越高。患者主要来源于农牧区,多数术前视力差。高度近视发病率较其他地区发病率低,而远视发病率较高。     

玻璃体切割联合白内障手术治疗增殖性糖尿病视网膜病变中的疗效

目的:探讨玻璃体切割联合白内障手术治疗增殖性糖尿病视网膜病变的疗效。方法:选择2013年1月至2016年6月我院接诊的90例增殖性糖尿病视网膜病变患者,通过随机数表法分为观察组(n=45)和对照组(n=45)。对照组使用玻璃体切割术+晶状体切除术,观察组使用玻璃体切割术+超声乳化吸除术。比较两组最佳矫正视力、泪液白介素(IL)-2、角膜荧光素染色(FL)、泪膜破裂时间(BUT)以及泪液分泌试验(SIt)的结果以及并发症的发生情况。结果:手术后,观察组最佳矫正视力明显优于对照组(P0.05),泪液IL-2水平明显高于对照组(P0.05),FL显著低于对照组,BUT、SIt明显高于对照组(P0.05),囊膜浑浊、虹膜新生血管、角膜水肿、干眼症的发生率均显著低于对照组(P0.05)。结论:玻璃体切割联合超声乳化吸除术治疗增殖性糖尿病视网膜病变患者的效果显著,可促进术后视力恢复,改善泪液分泌,并减少并发症。     

血塞通在23G微创玻切手术治疗糖尿病性玻璃体积血的作用

目的:探讨注射用血塞通(冻干粉)在23G微创玻切手术治疗糖尿病性玻璃体积血中的作用。方法:选取我院收治的2型糖尿病性玻璃体积血70例,将其随机分为两组,均给予常规血糖控制及23G微创玻切手术治疗,实验组于手术前给予注射用血塞通。对比两组患者的手术时间、术后并发症的发生率以及视力恢复情况。结果:实验组的平均手术时间明显短于对照组,术后出血、房性炎症、视网膜脱离、新生血管性青光眼并发症的发生率均明显低于对照组,差异有统计学意义(P0.05);实验组视力恢复的总有效率显著高于与对照组,差异有统计学意义(P0.05)。结论:术前应用注射用血塞通能够明显提高23G微创玻切手术治疗糖尿病性玻璃体积血的临床疗效,值得临床推广。     

社区获得性肺炎患者病原微生物特征CSCD

目的研究社区获得性肺炎患者病原微生物分布情况。方法选择2017年1月至2018年1月在本院急诊科治疗的确诊为社区获得性肺炎(CAP)的患者257例,采用自行设计的调查表研究患者基本资料,收集患者痰标本和血液标本进行微生物检测。结果入选患者中年龄≥60岁者比例明显高于18~44岁及45~59岁患者。年龄≥60岁的患者中高血压、冠心病、糖尿病、COPD、肾功能不全、入院前抗生素使用、BMI≤18.5,CURB-65≥2的比例明显高于18~44岁及45~59岁患者。嗜肺军团菌(11.28%)是患者最常见的病原体,其次为流感病毒(10.51%)。其余检出病原体为铜绿假单胞菌(9.34%)、大肠埃希菌(8.95%)、金黄色葡萄球菌(8.56%)、支原体(5.84%)、鲍曼不动杆菌(5.06%)、肺炎衣原体(5.06%)、阴沟肠杆菌(2.72%)、克雷伯杆菌(2.72%)、肺炎链球菌(2.72%),嗜麦芽假单胞菌(2.33%)、产气肠杆菌(1.17%)、流感嗜血杆菌(0.78%)、溶血链球菌(0.39%)。≥60岁患者中嗜肺军团菌、流感病毒、铜绿假单胞菌、大肠埃希菌、鲍曼不动杆菌感染的比例明显高于18~44岁及45~59岁患者。结论 CAP主要发病于60岁以上的患者,糖尿病、高血压、肾功能不全等合并症可能是CAP的危险因素。嗜肺军团菌、流感病毒、大肠埃希菌、铜绿假单胞菌、支原体、鲍曼不动杆菌等是CAP的主要病原微生物。     

Quantitative proteomics analysis of human vitreous in rhegmatogenous retinal detachment associated with choroidal detachment by data-independent acquisition mass spectrometry

The prognosis of rhegmatogenous retinal detachment (RRD) with choroidal detachment (RRDCD) is often poor and complicated. This study focused on the identification of the characteristic proteins and signal pathways associated with the etiology of RRDCD and to provide guidance for diagnosis and treatment of RRDCD. In this study, vitreous humor samples were obtained from 16 RRDCD patients, 14 with RRD, 12 with idiopathic epiretinal macular membrane (IEMM), and 5 healthy controls from donated corpse eyes. Data-independent acquisition mass spectrometry and bioinformatics analysis were employed to identify differentially expressed proteins (DEPs). In the vitreous humor, 14,842 peptides were identified. Patients with RRDCD had 249 DEPs (93 upregulated and 156 downregulated), with 89 in patients with RRD and 61 in patients with IEMM. Enrichment analysis of the GO and Kyoto Encyclopedia of Genes and Genomes DEP databases indicated functional clusters related to inflammation and immunity, protein degradation and absorption, cell adhesion molecules (CAMs), the hedgehog signaling pathway, and lipid metabolism. Weighted gene co-expression network analysis showed that DEPs with positive co-expression of RRDCD participated in immune-related pathways led by the complement and coagulation cascade, whereas DEPs with negative co-expression of RRDCD participated in protein degradation and absorption, CAMs, and the hedgehog signaling pathway. In summary, our study provides important clues and the theoretical basis for exploring the pathogenesis, progression, and prognosis of ocular fundus disease.

     

雷珠单抗与阿柏西普玻璃体腔注射治疗渗出性年龄相关性黄斑变性的疗效观察

目的:探究雷珠单抗与阿柏西普玻璃体腔注射治疗渗出性年龄相关性黄斑变性的临床疗效与安全性。方法:选取2015年5月～2018年5月我院收治的渗出性年龄相关性黄斑变性患者98例(98眼),采用随机数字表法将患者分为两组,A组玻璃体腔内缓慢注射0.05 m L(0.5 mg)雷珠单抗注射液,B组玻璃体腔内缓慢注射0.05 m L(2 mg)阿柏西普注射液。比较两组患者的视力改善情况、眼动脉血流动力学、黄斑中心凹视网膜厚度及不良反应的发生情况。结果:治疗前两组患者的视力比较无统计学差异(P0.05),治疗后,B组视力显著高于A组(P0.05);。两组患者治疗前后眼动脉血流动力学相关指标比较均无统计学差异(P0.05)。;两组患者治疗后的黄斑中心凹视网膜厚度均显著降低,且治疗3个月B组治疗3个月显著低于A组(P0.05);B组患者注射药物后结膜下大出血发生率显著低于A组(P0.05)。结论:阿柏西普可显著改善渗出性年龄相关性黄斑变性患者的视力,且安全性高,可能与其可显著改善患者的黄斑中心凹视网膜厚度有关,且不良反应发生率低,安全性好。     

Spontaneous ophthalmic lesions in young Swiss mice.

BACKGROUND AND PURPOSE: Outbred mice are frequently used in toxicity evaluation. Due to their small size, ophthalmologic examination of such animals is difficult with regard to restraint and use of instruments designed for human medicine. The clinical appearance and incidence of spontaneous ophthalmic lesions should be helpful in selecting mice for toxicity studies and allow distinction between intercurrent spontaneous ocular changes and those attributable to drugs or chemicals. METHODS: Pretest ophthalmologic examinations of about 3,000 4- to 5-week-old Swiss mice, Crl:CD1 (ICR)BR, conducted in 1995 and 1996, provided information about spontaneous ocular changes and their incidence. Eye evaluations were performed after pupil dilatation (0.5% tropicamide instillation), using indirect ophthalmoscopy, and when indicated, a portable slit lamp. RESULTS: Lenticular opacities and heterogeneity/prominence were the most common findings (up to 19%) in the anterior segment. Abnormalities of the cornea and iris were detected in up to 4% of mice. Hyaloid artery remnant, as well as isolated cases of floating bodies or hemorrhage, was observed in the vitreous of 12 to 17% of mice. Approximately 2 to 4% of mice had colobomatous fundus, retinal fold, or retinal atrophy. A few mice had chorioretinal atrophy, hemorrhage, or abnormal pattern of the retinal vasculature. Remaining findings consisted of incomplete palpebral fissure, microphthalmia, exophthalmia, ophthalmic hemorrhage, and scleral mass. CONCLUSIONS: Due to severity of the condition or interference with ocular examination, affected mice should be eliminated from experimental studies. Hence, pretest ocular examinations of mice are indicated in safety-assessment toxicity studies.     

Interleukin-1β Level Is Increased in Vitreous of Patients with Neovascular Age-Related Macular Degeneration (nAMD) and Polypoidal Choroidal Vasculopathy (PCV)

PurposeTo examine the expression of pro-interleukin-1β (pro-IL-1β) and interleukin-1β (IL-1β) in the vitreous body of patients with neovascular age-related macular degeneration(nAMD), polypoidal choroidal vasculopathy (PCV), proliferative diabetic retinopathy (PDR), retinal vein occlusion (RVO) or Eales’ disease to further elucidate the role of IL-1β and inflammation in the pathogenesis of neovascular retinal disease.DesignProspective clinical laboratory investigation study.MethodsAll patients enrolled had vitreous hemorrhage due to nAMD, PCV, PDR, RVO or Eales’ disease that required vitrectomy. Patients were excluded for any history of active intraocular inflammation, or other ophthalmic surgery besides vitrectomy. Control samples were obtained from patients with idiopathic macular epiretinal membrane. A total of fifty vitreous samples were collected from patient during vitrectomy. Pro-IL-1β and IL-1β expression were measured by enzyme-linked immunosorbent assay (ELISA). Results were analyzed statistically using nonparametric tests.ResultsExpression of pro-IL-1β protein was increased by 2.83-fold and 9.19-fold in PCV and nAMD vitreous samples relative to control, respectively. Expression of IL-β protein was increased by 10-fold and 4.83-fold in PCV and nAMD vitreous samples relative to control, respectively.ConclusionsOur results demonstrate that expression of pro-IL-1β and IL-1β proteins is higher in PCV and nAMD. The roles of pro-IL-1β and IL-1β as inflammatory mediators in the development of PCV and nAMD may be associated with photoreceptor degeneration and neovascularization which necessitates further study.     

Comprehensive Analysis of Inflammatory Immune Mediators in Vitreoretinal Diseases

Inflammation affects the formation and the progression of various vitreoretinal diseases. We performed a comprehensive analysis of inflammatory immune mediators in the vitreous fluids from total of 345 patients with diabetic macular edema (DME, n = 92), proliferative diabetic retinopathy (PDR, n = 147), branch retinal vein occlusion (BRVO, n = 30), central retinal vein occlusion (CRVO, n = 13) and rhegmatogenous retinal detachment (RRD, n = 63). As a control, we selected a total of 83 patients with either idiopathic macular hole (MH) or idiopathic epiretinal membrane (ERM) that were free of major pathogenic intraocular changes, such as ischemic retina and proliferative membranes. The concentrations of 20 soluble factors (nine cytokines, six chemokines, and five growth factors) were measured simultaneously by multiplex bead analysis system. Out of 20 soluble factors, three factors: interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1) were significantly elevated in all groups of vitreoretinal diseases (DME, PDR, BRVO, CRVO, and RRD) compared with control group. According to the correlation analysis in the individual patient''s level, these three factors that were simultaneously increased, did not show any independent upregulation in all the examined diseases. Vascular endothelial growth factor (VEGF) was significantly elevated in patients with PDR and CRVO. In PDR patients, the elevation of VEGF was significantly correlated with the three factors: IL-6, IL-8, and MCP-1, while no significant correlation was observed in CRVO patients. In conclusion, multiplex bead system enabled a comprehensive soluble factor analysis in vitreous fluid derived from variety of patients. Major three factors: IL-6, IL-8, and MCP-1 were strongly correlated with each other indicating a common pathway involved in inflammation process in vitreoretinal diseases.     

Rhegmatogenous Retinal Detachment Surgery in Elderly People over 70 Years Old: Visual Acuity,Quality of Life,and Cost-Utility Values

Background and Purpose

To evaluate the influence of rhegmatogenous retinal detachment (RRD) surgery on elderly patients in terms of visual acuity, vision-related quality of life and its cost-effectiveness.

Methods

Elderly patients over 70 years old, who were diagnosed and underwent RRD surgery at Shanghai First People''s Hospital, Shanghai Jiao Tong University, China, from January 1, 2009, through January 1, 2013. The participants received scleral buckling surgery and vitreous surgery with or without scleral buckling under retrobulbar anesthesia. We followed the patients for 1 year and collected best-corrected visual acuity (BCVA), vision-related quality of life, and direct medical costs data. Utility values elicited by time-trade-off were analyzed to determine the quality of life. Quality-adjusted life years (QALYs) gained in life expectancy were calculated and discounted at 3% annually. Costs per QALY gained were reported using the bootstrap method. Further analyses were made for two age groups, age 70–79 and age over 80 years. Sensitivity analyses were performed to test stability of the results.

Results

98 patients were included in the study. The BCVA significantly improved by 0.53±0.44 (Logarithm of the Minimum Angle of Resolution (logMAR)) at the 1-year postoperative time point (p<0.001). Utility values increased from 0.77 to 0.84 (p<0.001), and an average of 0.4 QALYs were gained in the life expectancy. Costs per QALY gained from the RRD surgery were 33,186 Chinese Yuan (CNY) (5,276 US dollars (USD))/QALY; 24,535 CNY (3,901 USD)/QALY for the age group of 70–79 years and 71,240 CNY (11,326 USD)/QALY for the age group over 80 years.

Conclusions

RRD surgery improved the visual acuity and quality of life in the elderly patients over 70 years old. According to the World Health Organization’s recommendation, at a threshold of willingness to pay of 115,062 CNY (18,293 USD)/QALY, RRD surgery is cost effective in the elderly patients.     

Increased Expression of Angiogenic and Inflammatory Proteins in the Vitreous of Patients with Ischemic Central Retinal Vein Occlusion

BackgroundCentral retinal vein occlusion (CRVO) is a common disease characterized by a disrupted retinal blood supply and a high risk of subsequent vision loss due to retinal edema and neovascular disease. This study was designed to assess the concentrations of selected signaling proteins in the vitreous and blood of patients with ischemic CRVO.MethodsVitreous and blood samples were collected from patients undergoing surgery for ischemic CRVO (radial optic neurotomy (RON), n = 13), epiretinal gliosis or macular hole (control group, n = 13). Concentrations of 40 different proteins were determined by an ELISA-type antibody microarray.ResultsExpression of proteins enriched in the vitreous (CCL2, IGFBP2, MMP10, HGF, TNFRSF11B (OPG)) was localized by immunohistochemistry in eyes of patients with severe ischemic CRVO followed by secondary glaucoma. Vitreal expression levels were higher in CRVO patients than in the control group (CRVO / control; p < 0.05) for ADIPOQ (13.6), ANGPT2 (20.5), CCL2 (MCP1) (3.2), HGF (4.7), IFNG (13.9), IGFBP1 (14.7), IGFBP2 (1.8), IGFBP3 (4.1), IGFBP4 (1.7), IL6 (10.8), LEP (3.4), MMP3 (4.3), MMP9 (3.6), MMP10 (5.4), PPBP (CXCL7 or NAP2) (11.8), TIMP4 (3.8), and VEGFA (85.3). In CRVO patients, vitreal levels of CCL2 (4.2), HGF (23.3), IGFBP2 (1.23), MMP10 (2.47), TNFRSF11B (2.96), and VEGFA (29.2) were higher than the blood levels (vitreous / blood, p < 0.05). Expression of CCL2, IGFBP2, MMP10, HGF, and TNFRSF11B was preferentially localized to the retina and the retinal pigment epithelium (RPE).ConclusionProteins related to hypoxia, angiogenesis, and inflammation were significantly elevated in the vitreous of CRVO patients. Moreover, some markers known to indicate atherosclerosis may be related to a basic vascular disease underlying RVO. This would imply that local therapeutic targeting might not be sufficient for a long term therapy in a systemic disease but hypothetically reduce local changes as an initial therapeutic approach.     

Dynamic Increase in Extracellular ATP Accelerates Photoreceptor Cell Apoptosis via Ligation of P2RX7 in Subretinal Hemorrhage

Photoreceptor degeneration is the most critical cause of visual impairment in age-related macular degeneration (AMD). In neovascular form of AMD, severe photoreceptor loss develops with subretinal hemorrhage due to choroidal neovascularization (CNV), growth of abnormal blood vessels from choroidal circulation. However, the detailed mechanisms of this process remain elusive. Here we demonstrate that neovascular AMD with subretinal hemorrhage accompanies a significant increase in extracellular ATP, and that extracellular ATP initiates neurodegenerative processes through specific ligation of Purinergic receptor P2X, ligand-gated ion channel, 7 (P2RX7; P2X7 receptor). Increased extracellular ATP levels were found in the vitreous samples of AMD patients with subretinal hemorrhage compared to control vitreous samples. Extravascular blood induced a massive release of ATP and photoreceptor cell apoptosis in co-culture with primary retinal cells. Photoreceptor cell apoptosis accompanied mitochondrial apoptotic pathways, namely activation of caspase-9 and translocation of apoptosis-inducing factor (AIF) from mitochondria to nuclei, as well as TUNEL-detectable DNA fragmentation. These hallmarks of photoreceptor cell apoptosis were prevented by brilliant blue G (BBG), a selective P2RX7 antagonist, which is an approved adjuvant in ocular surgery. Finally, in a mouse model of subretinal hemorrhage, photoreceptor cells degenerated through BBG-inhibitable apoptosis, suggesting that ligation of P2RX7 by extracellular ATP may accelerate photoreceptor cell apoptosis in AMD with subretinal hemorrhage. Our results indicate a novel mechanism that could involve neuronal cell death not only in AMD but also in hemorrhagic disorders in the CNS and encourage the potential application of BBG as a neuroprotective therapy.