低分子肝素缓释系统防治兔后发性白内障的实验研究

目的 探讨低分子肝素缓释系统防治兔后发性白内障的有效性和安全性.方法 采用前瞻性随机分组对照研究.以乳酸-羟基乙酸共聚物(PLGA)为载体采用冻干法制备低分子肝素缓释系统(LMWH DDS)并体外评价其缓释特性.将50只(50只眼)新西兰白兔分别行超声乳化透明晶状体吸除术,并随机均分为5组:A组术后生理盐水滴眼,B、C、D组术毕后房分别植入载药量为1.00 mg、0.50 mg、0.25 mg的LMWH DDS,E组植入不含药物的空白缓释系统;术后12周对术眼行裂隙灯显微镜、组织病理学以及电镜检查,并检测房水药物浓度和晶状体后囊膜湿重.术后房水闪光、房水细胞分级以及后囊膜混浊分级资料采用Kruskal-Wallis检验,房水药物浓度采用具有一个重复测量因素的两因素方差分析.结果 采用冻干法制备的LMWH DDS包封率为98.2%,体外释药方程拟合以零级方程为佳.术后B、C、D组炎症反应较A、E组显著减轻;术后12周A、B、C、D、E各组后囊膜混浊发生率分别为100%(10/10)、20%(2/10)、30%(3/10)、90%(9/10)、100%(10/10),后囊膜混浊分级评分组间比较差异均具有统计学意义(X~2=31.637,P=0.000),后囊膜湿重分别为(114.59±14.58)mg、(24.14±6.08)mg、(39.23±17.13)mg、(99.35±29.37)rag、(115.29±19.87)mg,组间比较差异均具有统计学意义(F=42.149,P=0.000);术后4周内B、C组房水中低分子肝素一直维持较高浓度(大于20 ms/L),D组浓度较低且不稳定;光镜和电镜下B、C组后囊细胞增生不活跃,未发现眼内毒性反应;术后均未见眼内出血现象.结论 以PLGA为载体采用冻干法制备的LMWHDDS具有良好的缓释性和组织相容性;其后房植入能明显减轻术后炎症反应,能安全、有效抑制后发性白内障的发生,且存在一定量效关系.     

肝素缓释系统抑制后发性白内障的实验研究

目的　探讨肝素缓释系统抑制后发性白内障发生的可行性和有效性。方法　将 30只(30只眼 )超声乳化透明晶状体吸除术后新西兰大白兔随机均分为A组 (术后生理盐水滴眼 )、B组(术中后房内植入空白缓释系统 )及C组 (术中后房内植入肝素缓释系统 )。术后 12周对 3个组兔眼进行裂隙灯显微镜、组织病理学及电镜检查 ,并检测血、房水肝素浓度和晶状体后囊膜的湿重。结果(1)术后 12周A、B及C组发生晶状体后囊膜混浊的眼数分别为 10、10及 4只眼 ,差异有非常显著意义(χ2 =14 0 9,P =0 0 0 1)。 (2 )术后 12周A、B及C组晶状体后囊膜的平均湿重分别为 (15 8± 5 )、(16 0± 9)及(2 0± 3)mg,差异有非常显著意义 (F =116 8 99,P =0 0 0 0 )。 (3)C组房水中的平均肝素浓度为 (2 6± 12 )mg/L。 (4)光镜和电镜下C组兔眼晶状体后囊膜细胞增殖不活跃 ,未发现眼内毒性反应。 (5 )术中和术后无眼内出血现象。结论　后房内植入肝素缓释系统 ,可明显提高并长期维持房水中的肝素浓度 ,有效抑制后发性白内障的发生 ;该方法毒副作用小 ,是一种安全、有效的给药方式。     

Polylactide-glycoli acid and rapamycin coating intraocular lens prevent posterior capsular opacification in rabbit eyes

Objectives  Posterior capsular opacification (PCO) is caused by the proliferation and migration of residual lens epithelium cells (LECs) after extracapsular cataract extraction (ECCE). Rapamcin (RAPA) is known to be a potent immunosuppressive drug with anti-inflammatory and anti-proliferative effects. The aim of this study was to investigate the safety and efficacy of rapamycin sustained release from modified intraocular lens (IOLs) in the prevention of PCO in rabbits. Methods  Three types of IOLs were used, including the original IOL without modification, IOL with polylactide-glycoli acid (PLGA) coating (PLGA-IOL), and RAPA-loaded PLGA-IOL (RAPA-PLGA-IOL). Sixty New Zealand albino rabbits undergoing phacoemulsification in left eyes were randomly and equally divided into three groups. Group A was implanted with the original IOLs, group B was implanted with the PLGA-IOLs, and group C was implanted with the RAPA-PLGA-IOLs. All of the 60 treated left eyes were examined by a slit-lamp microscope. The concentrations of RAPA in the aqueous humor and blood were determined by high-performance liquid chromatography (HPLC), indicating an vivo release of drug from the polymer carrier. Anterior segment tissue was histologically examined, and wet posterior capsules were weighed. Six months after intervention the PCO was graded. Results  The mean concentrations of RAPA in the aqueous humor from group C at 2 h, 1 days, 3 days, and 7 days after operation were 12.81 ± 1.27 μg/ml, 14.57 ± 0.99 μg/ml, 6.39 ± 0.95 μg/ml, and 1.10 ± 0.32 μg /ml respectively. The concentrations of RAPA in blood were undetectable. During the early days after the operation, the reactions of the anterior chamber from groups A and B were more severe than from group C. Our findings showed that the initial appearance of PCO in group C was much later than in the other two groups. The wet posterior capsules were weighed to be 0.3735 ± 0.0943 g (group A), 0.3754 ± 0.1093 g (group B), and 0.0432 ± 0.0089 g (group C). Histological observation showed a similar phenomenon, that there was remarkably less accumulation of lens materials on the posterior capsules in group C than in the other two groups. Conclusion  Our findings suggest that the designed RAPA-PLGA-IOL effectively prevented formation and development of PCO for a relatively long duration.     

FK506缓释系统前房植入抑制兔高危角膜移植术后的免疫排斥反应

目的探讨前房植入FK506药物缓释系统（DDS）对兔高危角膜移植术后免疫排斥反应的抑制作用和FK506房水药物浓度与免疫排斥反应的关系。方法107只新西兰白兔中随机数字法选取73只兔进行角膜新生血管化模型的制作,其中68只兔作为受体成功建立高危角膜移植动物模型,随机数字法分为对照组、空白DDS前房植入组、环孢素A（CsA）DDS前房植入组（含CsA 1mg）、0．1％FK506眼液滴眼组及FK506 DDS前房植入组（含FK5060．5mg）。角膜移植术后观察各组角膜植片排斥发生的时间,移植术后1周取各组实验兔眼房水和静脉血进行FK506药物浓度检测。0．1％FKS06眼液滴眼组和FKS06 DDS前房植入组在移植术后的不同时间点抽取实验兔眼房水和静脉血,进行FK506药物浓度的检测。观察各组兔移植术后4周和观察期结束时角膜植片的病理变化,同时应用原位杂交的方法检测各组角膜植片内白细胞介素2受体a（IL-2Bot）、单核细胞趋化蛋白1（MCP-1）、Fas及FasL mRNA的表达。结果FK506 DDS前房植入组角膜植片存活时间超过180d,明显优于其他各组（F=926．37,P=0．0000）,其房水和角膜组织中的FK506药物浓度明显高于FKS06眼液滴眼组（T=21．00,P=0．0022）。FKS06 DDS前房植入组在术后24周内均能在房水中检测出FK506。术后4周对照组和空白DDS前房植入组有大量的炎性细胞浸润,并有明显的IL．2Bet和MCP-1mRNA的表达,而CsADDS前房植入组、FK506眼液滴眼组及FK506 DDS植入组角膜未见明显的炎性细胞浸润,未见IL-2Pux和MCP-1mRNA的表达。各组均未见明显的Fas和FasL mRNA的表达。结论前房植入FK506 DDS可有效地抑制高危角膜移植术后免疫排斥反应的发生,房水中较高的FK506药物浓度是防治术后发生免疫排斥反应的重要因素。     

肝素表面处理人工晶状体在并发性白内障手术中应用疗效观察

目的探讨肝素表面处理人工晶状体在并发性白内障患者手术中应用的疗效。方法106例(152只眼)并发性白内障患者中随机抽取98只眼为研究组(A),植入HQ-201HEP型肝素表面处理人工晶状体;54只眼为对照组(B),植入MA-60MB型人工晶状体。比较术后视力、眼压、前房闪辉、房水细胞、虹膜后粘连、后囊膜混浊等结果。结果研究组(A)中98只眼有前房闪辉30只眼(30.6%),房水细胞阳性26只眼(26.5%),虹膜后粘连17只眼(17.3%),后囊膜混浊2只眼(2.04%),高眼压2只眼(2.04%)。而对照组(B)54只眼有前房闪辉42只眼(77.8%),房水细胞阳性43只眼(79.6%),虹膜后粘连24只眼(44.4%),后囊膜混浊7只眼(12.7%),高眼压6只眼(11.1%)。结论临床研究发现肝素表面处理人工晶状体在减轻眼内炎症反应、异物反应、细胞在人工晶状体表面沉着(前房闪辉、房水细胞、虹膜后粘连、后囊膜混浊)等方面优于对照组,尤其对于有葡萄膜炎病史、青光眼术后、局部和全身应用类固醇激素者尤为适合,可减轻高眼压和前房出血的发生。     

雷帕霉素缓释片防治兔高危角膜移植免疫排斥反应和新生血管增殖的研究

目的探讨雷帕霉素(RAPA)缓释片防治兔高危角膜移植术后免疫排斥反应和角膜新生血管增殖的疗效及其作用机制。方法RAPA缓释片制作:RAPA与载体乙交酯-丙交酯-己内酯三元共聚物(PGLC)制成RAPA缓释片(W/W=50/50),每粒缓释片含RAPA0·5mg。65只健康新西兰大白兔,其中45只兔(45只眼)采用缝线法诱导角膜新生血管生成,选择大于3个象限、新生血管长入角膜超过3mm的40只兔按照随机数字表法分为对照组(A组)、1mgPGLC载体前房植入组(B组)、1%RAPA滴眼液组(C组)及0·5mgRAPA缓释片前房植入组(D组),每组10只兔;余20只兔为供体。对4组兔行右眼同种异体穿透性角膜移植术,术后观察90d,记录排斥指数(RI,为植片水肿、混浊及血管长入评分合计)和新生血管指数(NI,为血管长入植片评分)。定期检测C、D组兔房水中RAPA浓度;术后3周,原位杂交法对4组兔角膜植片中白细胞介素(IL)-2R、单核细胞化学吸引蛋白质(MCP)-1、Fas/FasL进行检测,采用免疫组化法对肿瘤坏死因子(TNF)α和血管内皮细胞生长因子(VEGF)进行检测。术后90d,病理组织学检查视网膜、肝肾结构变化。结果(1)免疫排斥:A、B、C及D组兔发生免疫排斥反应的平均时间分别为(16·5±2·5)、(16·0±2·6)、(47·1±13·2)、(87·6±5·8)d(P=0·000)。术后2周,4组兔植片RI分别为4·9±2·2、3·9±0·9、0·8±0·4、0·3±0·6(P=0·000)。术后12周分别为10·4±0·8、10·0±0·0、7·2±2·2、2·0±3·3(P=0·000)。(2)角膜新生血管:术后2周,4组NI数分别为2·4±0·7、2·1±0·5、0·6±0·5、0·3±0·5(P=0·000)。术后12周分别为3·8±0·5、3·8±0·4、0·8±0·7、0·4±0·8(P=0·000)。(3)房水中RAPA浓度:术后第2、4、8、12周,D组房水中RAPA浓度分别10·7、12·0、9·2、7·0ng/ml,C组房水中RAPA浓度检测不出。(4)细胞因子表达:A、B组植片大量表达IL-2R、MCP-1、TNF-α、VEGF细胞因子,C、D组不表达上述细胞因子,4组植片中Fas/FasL均不表达。(5)组织病理:4组兔视网膜、肝肾组织结构正常。结论局部应用RAPA可以防治兔高危角膜移植术后免疫排斥反应和角膜新生血管增殖,RAPA缓释片疗效优于滴眼液。     

Prevention of posterior capsule opacification by retinoic acid and mitomycin

BACKGROUND: Our aim was to evaluate the effect of an intraoperative single dose of retinoic acid (RA) or mitomycin C (MMC) in preventing posterior capsule opacification (PCO). METHODS: Twenty-seven rabbits were divided randomly into three groups. RA (250 microg/ml) and MMC (0.04 mg/ml) were given 0.1 ml by hydrosection and 0.9 ml into the capsular bag after phacoemulsification. The third group served as a control group. Three months after intervention PCO was graded clinically. Furthermore, proliferation of lens epithelial cells was evaluated histologically. RESULTS: Two eyes developed corneal edema in the MMC group. On clinical assessment, RA and MMC were significantly effective in preventing PCO compared with controls (P<0.005). On histological analysis, there was significantly reduced proliferative activity on posterior capsules in the treatment groups, in contrast to multilayer cells in the control group. CONCLUSION: Intraoperative single-dose administration of RA and MMC significantly prevented the development of PCO in rabbit eyes. The optimal biocompatible dosage must be carefully determined by further investigation.     

IL-1ra-壳聚糖缓释剂对兔后发性白内障的抑制作用

目的:探讨IL-1ra-壳聚糖缓释剂对兔眼晶状体囊外摘除术后房水中炎性细胞因子IL-1含量及后囊膜混浊的影响。方法:将健康日本大耳白兔30只随机分为A,B,C3组,对右眼30只均行透明晶状体囊外摘除术,术中囊袋内分别注入缓冲液0.1mL(A组),注入5g/LIL-1ra0.1mL(B组),置入IL-1ra-壳聚糖缓释剂一粒(C组)。分别于术后1,3,7,14,28,56,84d抽取房水0.1~0.2mL,用酶联免疫吸附试验(ELISA)方法测定IL-1的含量。定期裂隙灯显微镜观察角膜,前房及晶状体后囊膜混浊情况,术后84d处死白兔,做病理标本,行光镜及电镜检查。结果:术后84dA,B,C组之间后囊膜混浊情况差别有显著意义(P<0.01)。房水中IL-1含量测定表明B组较A组IL-1峰值明显降低;C组与A组IL-1含量差异显著,且C组呈持续下降趋势。光镜观察A组晶状体上皮细胞增生并有多层皮质纤维出现,B组偶见晶状体上皮细胞,C组晶状体后囊膜增生不活跃,囊膜光滑,后囊表面几乎无细胞及纤维蛋白粘附。结论:IL-1ra-壳聚糖缓释剂具有抑制兔眼后发性白内障的作用,较单纯用IL-1ra作用明显。     

前房植入环孢素A缓释系统抑制鼠高危角膜移植术后的免疫排斥反应

目的　探讨前房内植入环孢素A缓释系统 (cyclosporineAdrugdeliverysystem ,CsADDS)抑制高危角膜移植术后免疫排斥反应的有效性和可行性。方法　 (1)对 6 0只Wistar大鼠 (6 0只眼 )用缝线法诱导角膜新生血管增生。 (2 )将发生角膜新生血管化的 4 0只Wistar大鼠 (40只眼 )随机分为4组 :对照组 ,1%CsA滴眼组 ,CsADDS结膜下植入组 ,CsADDS前房内植入组。每组均接受同种异系(Spregue Dawley大鼠 )角膜供体 ,行穿透性角膜移植术 ,术后比较各组大鼠免疫排斥反应发生的时间 ,并定期检测各组大鼠房水中CsA的浓度。 (3)正常Wistar大鼠 8只 (16只眼 ) ,随机分为 2组 ,分别在结膜下和前房内植入CsADDS ,术后 2和 4周行眼的组织病理学检查。结果　 (1) 5 1只Wistar大鼠 (5 1只眼 )经角膜基质缝线 ,成功诱导角膜新生血管增生。 (2 ) 4组共 4 0只Wistar大鼠角膜移植术后免疫排斥反应的发生时间分别为 :对照组 (8 2 0± 1 4 8)d ,1%CsA滴眼组 (10 6 0± 1 90 )d ,CsADDS结膜下植入组 (11 4 0± 2 5 0 )d ,CsADDS前房内植入组 (17 0 0± 6 0 5 )d。房水中CsA浓度均值分别为 :对照组 0 μg/L ;1%CsA滴眼组 (47 90± 3 4 8) μg/L ;CsADDS结膜下植入组术后 1、2、4周 ,房水中CsA浓度均值分别为 (5 9 0 0± 3 6 6 ) μg/     

环孢素A缓释系统的眼内释药性和生物相容性的实验研究

目的研究前房植入环孢素A缓释系统(CsA DDS)的生物相容性和房水药物浓度变化。方法新西兰白兔36只,随机分为A、B、C、D四组,分别与A、B、C、D四型不同的CsA DDS相对应。每组9只兔随机编号为1～9号,其中1～3号兔各任选1只眼前房植入相应的CsA DDS,另1只眼植入不含CsA的空白缓释系统(EMDDS)为对照;4～6号兔各任选1只眼前房植入EM DDS,另1只眼行角膜切开及缝合术为对照;7～9号兔各任选1只眼前房植入CsA DDS,另1只眼行角膜切开及缝合术为对照。术后观察12周。结果四型CsA DDS均未见明显眼内毒性反应;A、B两型释药速率迅速,但维持时间短,C、D两型则缓慢而持久。结论前房植入CsA DDS对兔眼的生物相容性良好;4型CsA DDS中A、B型较适宜治疗排斥反应,C、D型较适宜预防排斥反应。     

Prevention of experimental proliferative vitreoretinopathy with a biodegradable intravitreal drug delivery system of all-trans retinoic acid

PURPOSE: To evaluate the antiproliferative effect of an all-trans retinoic acid (at-RA) drug delivery system (DDS) on experimental proliferative vitreoretinopathy (PVR). METHODS: PVR was induced in rabbits with core vitrectomy and fibroblast injection. The DDS containing 420 microg, 650 microg, and 1,070 microg of at-RA was implanted into the vitreous of treated groups B, C, and D, respectively. Group A with no DDS and group E with nonmedicated DDS served as controls. The intravitreal at-RA concentration was measured with high-pressure liquid chromatography. The drug toxicity was evaluated histologically. RESULTS: The severity of PVR was significantly reduced in groups C and D but not in groups A, B, and E. The drug release peaked at 6 weeks to 7 weeks. No signs of retinal toxicity were found in the DDS groups. CONCLUSION: Intravitreal implantation of at-RA DDS appears effective in inhibiting the development of PVR and is well tolerated in rabbit eyes.     

两性霉素B缓释系统治疗兔烟曲霉菌眼内炎的药效学实验研究

目的探讨两性霉素B缓释系统（AmB—DDS）玻璃体腔植入对烟曲霉菌性眼内炎的疗效、AmB-DDS的药物释放规律及最佳释药量。方法选取40只新西兰白兔作为实验动物。（1）Amb-DDS治疗烟曲霉菌性眼内炎疗效学观察：动物玻璃体腔内注入烟曲霉菌悬液,48h后随机分为5组,A组为空白对照组（6只眼）,B组为空白DDS组（6只眼）,C组为两性霉素B玻璃体腔内注射组（6只眼）,D组为AmB—DDS250μg植入联合玻璃体切除术组（8只眼）,E组为AmB—DDS500μg植入联合玻璃体切除术组（8只眼）。术后不同时间点检测前房闪辉、细胞及玻璃体混浊程度,取玻璃体腔内容物行涂片检查和真菌培养,2个月时取眼球标本行病理学检查;（2）AmB—DDS玻璃体腔内药物浓度检测：H组玻璃体切除术后植入500μg AmB—DDS1个（6只眼）,术后第1、3、7天及2、4、6、8周取玻璃体液,高效液相色谱分析法检测药物浓度。结果A、B组全部发生严重眼内炎,伴眶内感染,组间比较差异无统计学意义（P〉0．05）;C、D、E组炎性反应较A、B组轻,差异有统计学意义（P≤0．005）;E组玻璃体混浊程度较C组轻,7～14d前房反应较C组轻,差异均有统计学意义（P≤0．005）;D组5只眼、E组8只眼治愈,差异有统计学意义（x^2=10．494,P=0．003）。不同时间点取玻璃体腔内容物涂片,所有标本6周内均见菌丝,真菌培养仅A、B组为阳性。病理学检查示治愈眼结构正常,感染未控制眼均萎缩,球壁结构被破坏。H组术后第1天即有释药,药物浓度迅速升高超出有效抑菌浓度,观察期内释药较平稳。结论AmB—DDS玻璃体腔内植入治疗烟曲霉菌性眼内炎安全有效,释药恒定,速率得当;以含药量为500μg的AmB—DDS治疗效果最佳。（中华腰科杂志,2007,43：546-553）     

FK506 in a biodegradable glycolide-co-clatide-co-caprolactone polymer for prolongation of corneal allograft survival

PURPOSE: FK506 has been extensively used in preventing immune rejection for human organ transplantation. This study aimed to evaluate the effects of a biodegradable FK506 drug delivery system (DDS) implanted into anterior chamber for the prolongation of corneal allograft survival in high-risk keratoplasty. METHODS: Biodegradable glycolide-co-clatide-co-caprolactone polymer (PGLC) was used as drug carrier to be incorporated with 0.5 mg of FK506 powder. The drug release from the FK506-PGLC DDS was evaluated in vitro and in vivo. The FK506-PGLC DDS was implanted into the anterior chamber of 12 high-risk keratoplasty rabbits. The graft survival time and clinical features of the FK506-PGLC DDS group were compared with the untreated, PGLC DDS, cyclosporin A-PGLC DDS, and 0.5% FK506 drops groups. The histopathological examination was performed to evaluate the safety of the FK506-PGLC DDS. RESULTS: The mean graft survival time was longest (> 180 days) in the FK506-PGLC DDS group. In vivo, the FK506 concentration in aqueous humor peaked on day 28 (17.9 +/- 2.3 ng/ml) and kept a sustained release for at least 168 days. No adverse reactions were observed in the FK506-PGLC DDS group. CONCLUSIONS: Biodegradable FK506-PGLC DDS implanted into anterior chamber can effectively prevent immune rejection in high-risk keratoplasty model, presenting a promising approach for the prolongation of corneal allograft survival.     

汉防己甲素抑制兔晶状体后囊膜混浊

目的 探讨汉防己甲素对白内障摘除术后晶状体后囊膜混浊形成的影响及其作用机制。方法 对48只实验兔行单眼囊外晶状体摘除及人工晶状体植入术。术前随机分为A组对照、B组术后结膜下注射地塞米松、C组术后结下注射汉防己甲素和D组术中植入汉防己甲素镀膜人工晶状体。术后不同时间检测各组术眼的房水细胞数、蛋白质和丙二醛含量,记录晶状体后囊膜混浊程度和湿重。结果 除术后14d房水丙二醛含量外,囊外晶状体摘除术后不同时间4个组的房水细胞数、蛋白质和丙二醛含量,以及晶状体后囊膜混浊的程度和湿重差异均有显著意义（P＜0．05）。其中B和C组术后不同时间房水细胞数、蛋白质和丙二醛含量均低于A组,差异有显著意义（P＜0．05）;B、C和D组术后不同时间晶状体后囊膜混混的程度和湿重均低于A组,差异有显著意义（P＜0．05）。结论 防汉己甲素可有效抑制兔眼晶状体摘除术后晶状体后囊膜混浊的形成;其最佳用药剂量和途径尚需深入探讨。     

环孢素A缓释系统眼内植入治疗葡萄膜炎的实验研究

目的探讨环孢素A缓释系统(CsA DDS)玻璃体腔植入治疗实验性葡萄膜炎的有效性和安全性。方法43只新西兰白兔中,其中30只建立葡萄膜炎动物模型,按照随机数字表法分为4组,即空白对照组(A)6只、空白DDS植入组(B)6只、CsA口服治疗组(C)6只及CsA DDS植入组(D)12只,于术后不同时间点观察各组兔眼前房闪辉、房水细胞、前房渗出、玻璃体细胞以及玻璃体混浊度并进行分级,并进行视网膜电图(ERG)、眼和肝、肾组织病理学检查;余13只新西兰兔右眼植入CsA DDS,检测玻璃体腔CsA药物浓度。结果(1)30只实验兔均成功诱发葡萄膜炎模型。各时间点A、B、C组各项炎性指标分级均高于D组,A、B组间及C、D组间差异无统计学意义(P>0.05),D组与A、B组间差异有统计学意义(P<0.05);ERG检查显示A、B两组b波波幅降低幅度均较D组明显,差异有统计学意义(P<0.05);A、B组睫状体和视网膜有大量炎性细胞浸润,组织明显破坏,而C、D组则未见炎性细胞浸润,组织结构基本完整。(2)CsA DDS植入术后玻璃体腔药物浓度在1个月时达到(491.0±481.6)ng/ml,2个月时为(575.2±373.2)ng/ml,3个月时缓慢下降至(301.5±128.5)ng/ml。光镜检查未见眼内毒性反应。结论CsA DDS玻璃体腔植入能够在眼内维持安全有效的药物浓度,明显减轻兔眼葡萄膜炎性反应,为葡萄膜炎的治疗提供了一种新的用药途径。     

葡萄膜炎并发白内障术中植入肝素修饰人工晶状体

目的评价葡萄膜炎并发白内障术中植入肝素表面修饰的PMMA人工晶状体的效果。方法98例（146眼）葡萄膜炎并发白内障行超声乳化吸出术,术中分别植入肝素修饰的PMMA人工晶状体56例（98眼）（肝素组）和未修饰PMMA人工晶状体42例（48眼）（对照组）。对两组术后视力、眼前段反应、后囊浑浊情况进行回顾性对比分析。结果矫正视力≥0．5者,肝素组86眼（87．76％）,对照组27眼（56．25％）,（P〈0．05）。眼前段反应：人工晶状体表面纤维素样渗出、房水细胞,均在术后1周时差异最显著（P〈0．05）,虹膜后粘连在6个月后两组差异最显著（P〈0．05）。后囊浑浊发生率6个月后对照组明显高于肝素组,分别为54．17％和12。24％（P〈0．05）。结论葡萄膜炎并发白内障术中植入肝素修饰人工晶状体能显著减轻术后眼前段的炎症反应,降低后囊浑浊的发生率。     

Application of sustained delivery microsphere of cyclosporine A for preventing posterior capsular opacification in rabbits

AIM: To explore the inhibitory effect of a sustained cyclosporin A (CsA) delivery microsphere (CsA-MS) on posterior capsular opacification (PCO) in rabbit eyes after cataract extraction.METHODS: Twenty New Zealand white rabbits accepted cataract extraction plus intraocular lens implantation and their left eyes were intraoperatively injected CsA-MS prepared using polymer polylactioglycolic acid (PLGA) as a carrier and their right eyes were injected with empty MS. The changes in cornea, anterior chamber reaction, intraocular pressure, PCO and CsA concentration in aqueous humor were examined postoperatively and all the eyes were enucleated 3 months after surgery for histopathological and morphological examination with light microscopy and electron microscopy.RESULTS:Conjunctival hyperemia, corneal edema, intraocular pressure and anterior chamber response of experimental and control eyes were similar, while PCO in CsA-MS injected eyes was greatly improved compared with that in control eyes. Posterior capsules in CsA-MS injected eyes were smooth and lens epithelial cells (LEC) did not proliferate significantly (P>0.05), while LEC in posterior capsule of control eyes had different degrees of proliferation and cortical regeneration. LEC in CsA-MS injected eyes were not functionally active and underwent apoptosis, whereas LEC in control eyes were functionally active (F-test, P=0.025). In addition, the corneal ultrastructure showed no differences between CsA-MS and MS injected eyes.CONCLUSION: CsA-MS has high bioavailability in rabbit eyes and could inhibit postoperative PCO occurrence and development during the study period, suggesting that CsA-MS may be a promising, effective and safe administration route to prevent PCO in clinic.     

Comparison of posterior capsule opacification in rabbit eyes receiving different administrations of rapamycin

Background

Posterior capsule opacification (PCO) is a common complication after cataract surgery. The purpose of this study was to determine the effects of three administering ways of rapamycin (RAPA) on the formation of PCO in rabbit eyes for 12 weeks.

Methods

Eighty rabbits were divided into four groups, according to the different administrations of RAPA which they received. These were: (1) the control group, (2) the irrigation-treated group — 5 ng/ml intraoperative RAPA irrigation solution, (3) the eye-drop-treated group — 2 mg/ml RAPA eye drops, and (4) the IOL-treated group — RAPA–poly(lactic-co-glycolic) acid (PLGA) loaded on the surface of intraocular lens (IOLs) (RAPA-PLGA-IOLs). All right eyes were treated with lens extraction plus IOL implantation, receiving relative administrations of RAPA. RAPA concentrations in the aqueous humour were determined by high performance of liquid chromatography (HPLC). The anterior chamber (AC) response was observed through slit-lamp biomicroscopy. After 12 weeks, the degree of PCO was determined by clinical evaluation. The histological sections, immunohistochemistry expression of proliferating cell nuclear antigen (PCNA) in the lens capsule were conducted.

Results

In the early period, AC response for both experimental and control eyes were similar. In the IOL-treated group, RAPA reached its peak at 25.68?±?0.74 μg/ml on the 4th day, and it was detectable until 8 weeks afterwards. However, in the other groups, RAPA could not be detected all the time. Compared with other groups, in the IOL-treated group, PCO was greatly alleviated; only a few layers of the lens epithelial cells (LECs) and a little proliferative material around the posterior capsules, and a significantly weak expression of PCNA in the nuclei of LECs. By contrast, there was no significant statistical difference in eye-drop-treated or irrigation-treated eyes and control eyes respectively.

Conclusions

Intraocular RAPA-PLGA-IOL was a promising, effective, and safe administration to prevent PCO compared with other methods in the rabbit PCO model.     

糖尿病对后发性白内障的影响及可能机制的初步研究

目的　探讨２型糖尿病对后发性白内障的影响及其可能的分子机制。方法　收集１０８例（１０８眼）白内障患者房水并行ＥＬＩＳＡ检测房水中ＩＬ-６含量,其中对照组（年龄相关性白内障患者）５０例（５０眼）,试验组（２型糖尿病白内障患者）５８例（５８ 眼）,比较两组最佳矫正视力、眼压、后发性白内障（ｐｏｓｔｅｒｉｏｒｃａｐｓｕｌｅｏｐａｃｉｆｉｃａｔｉｏｎ,ＰＣＯ）发生率、ＰＣＯ严重程度、房水中ＩＬ-６含量等。结果　白内障超声乳化联合人工晶状体植入术均提高了两组患者术后最佳矫正视力,且对照组较试验组最佳矫正视力提高明显（Ｐ＝０．００２）。对照组术前、术后眼压分别为（１３．９３±３．２５）ｍｍＨｇ（１ｋＰａ＝７．５ｍｍＨｇ）、（１４．６０±４．３５）ｍｍＨｇ,差异无统计学意义（Ｐ＞００５）;试验组术前、术后眼压分别为（１４．１８±３．５６）ｍｍＨｇ、（１５．１２±４．６６）ｍｍＨｇ,差异无统计学意义（Ｐ＞ ００５）。对照组ＰＣＯ发生率２６．００％,试验组ＰＣＯ发生率４１．３８％,两组间ＰＣＯ发生率差异无统计学意义（Ｐ＝０．０９５）。试验组房水中ＩＬ-６含量与后发性白内障呈正相关（ｒ＝０７３１,Ｐ＝０００１）,且试验组房水中ＩＬ-６含量较对照组明显升高（Ｐ＝００１２）。结论　房水中ＩＬ-６含量可能促进了糖尿病患者ＰＣＯ的发生发展,其具体机制尚需进一步研究。     

The effect of long-term use and inflammation on the ocular penetration of topical ofloxacin.

PURPOSE. To study the penetration of ofloxacin into the aqueous and vitreous humors after long-term topical administration and to investigate the effects of inflammation on drug penetration in rabbits. METHODS. A standardized model of intraocular infection after penetrating injury was achieved in the right eyes of 16 rabbits. The animals were randomly and equally divided into two groups. The intact left eyes of the groups were maintained as the control. Ofloxacin eyedrops (0.3%) were instilled into all eyes at a frequency of 2 drops every hour for 7 hours in the first group and for 14 hours in the second group. Half an hour after the last drop, samples of the aqueous and vitreous humors were taken and ofloxacin concentrations were measured by using HPLC. RESULTS. The mean aqueous humor concentrations of ofloxacin in control eyes after 7 and 14 hours of instillation were: 1.45 +/- 0.93 microg/ml and 2.48 +/- 0.33 microg/ml, respectively; those in infected eyes 2.35 +/- 1. 84 microg/ml and 3.49 +/- 1.47 microg/ml, respectively. However the differences among the groups were not significant (p > 0.05). The vitreous ofloxacin concentrations in the control eyes were similar after 7 and 14 hours of instillation (0.23 +/- 0.14 microg/ml, 0.27 +/- 0.10 microg/ml, respectively). In infected eyes, the mean vitreous ofloxacin concentration after 14 hour of instillation was significantly higher than that in control eyes (p < 0.05; 0.4 +/- 0. 09 microg/ml, 0.29 +/- 0.11 microg/ml, respectively). The mean vitreous ofloxacin concentration in infected eyes after 14 hours instillation was not significantly higher than that after 7 hours instillation. CONCLUSIONS. Topical ofloxacin instillation for 7 or 14 hours yields aqueous concentrations above the MIC(90) for common ocular pathogens. Prolonged application and the presence of inflammation increased the penetration of ofloxacin into the vitreous humor.