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 cornealultrastructure 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.

“NIR-triggered ROS storage”photodynamic intraocular implant for high-efficient and safe posterior capsular opacification prevention

Posterior capsular opacification(PCO)is the leading cause of vision loss after cataract,mainly caused by the adhesion,proliferation and trans-differentiation of post-operative residual lens epithelial cells(LECs).Effective PCO prevention remains a huge challenge to ophthalmologists and researches for decades.Herein,we developed a“NIR-triggered ROS storage”intraocular implant(CTR-Py-Pp IX)based on capsular tension ring(CTR),which is concurrently linked with photosensitizer protophorphyrin IX(Pp IX)and energy storage2-pyridone derivative(Py),to guarantee instantaneous and sustainable ROS generation for LECs killing,aiming to achieve more efficient and safer photodynamic therapy(PDT)to effectively prevent PCO.The silylated Pp IX-Si and Py-Si were covalently conjugated to the plasma activated CTR surface to obtain CTR-Py-Pp IX.Results demonstrated that CTR-Py-Pp IX had dual functions of PDT and battery,in which Pp IX could generate ROS extracellularly under irradiation,with one part directly inhibiting LECs by lipid peroxidation(LPO)induction of cell membranes.Meanwhile,the excess ROS stored in Py could be continuously released to amplify LPO levels after the irradiation was removed.Ultimately,the proliferation of LECs in capsular bag was completely inhibited under mild irradiation conditions,achieving a sustainable and controlled PDT effect for effective PCO prevention with good biocompatibility.This NIR-triggered ROS storage intraocular implant would provide a more efficient and safer approach for long-term PCO prevention.

Experimental study on cyclosporine A drug delivery system in prevention of posterior capsule opacification after intraocular lens implantation in rabbits

Objective To study the effect of cyclosporine A drug delivery system (CsA-DDS) on the prevention of posterior capsule opacification (PCO) after experimental intraocular lens implantation in rabbit eyes. Methods Twenty healthy New Zealand white rabbits, whose left eyes and right eyes were used respectively as experiment eyes and controls, were subjected to extracapsular lens extraction and artificial lens implantation. During the operation, CsA-DDS with poly (lactideco-glycolide) as carriers or empty DDS was implanted in the capsular bag for the experimental eyes and controls respectively. After the operation, anterior chamber reaction, intraocular pressure (IOP) and CsA concentration were monitored and twelve weeks after the operation, the eyes were extracted for histopathological and morphological examinations. Results There were no differences between the two groups in conjunctival congestion, IOP change and anterior chamber reaction. PCO was less severe in the experimental eyes than in the controls. Light microscopy revealed that posterior capsular membrane in the experimental eyes was slick, with no obvious proliferation, whereas in the controls, there were lens epithelial cell proliferation and cortex regeneration of different degrees. Morphological examination with electron microscope showed that in the experimental eyes, lens epithelial cells did not function actively and apoptosis occurred, whereas in the controls, epithelial cells presented active function. No marked ultrastructural changes were found in either group. Conclusion Cs-DDS can inhibit PCO after intraocular lens implantation in rabbit eyes and does not have toxic effects on the surrounding ocular tissues. Therefore, it has a good potential for clinical use in prevention of PCO.

Effect of Liposome-Encapsulated Total Alkaloid of Harmaline on Rabbit Lens Epithelial Cells:Experimental Study on the Prevention of Posterior Capsule Opacification

Purpose: To investigate whether liposome encapsulated total alkaloid of Harmaline (TAH) as a therapeutic agent is beneficial to prevention of posterior capsular opacifi-cation (PCO).Methods: Liposome-encapsulated TAH was prepared by modified freeze-thawing method. 0. 1ml of liposome-encapsulated TAH (0. 2mg/ml) was injected into the capsular bag during extracapsular lens extraction (ECLE) of each eye in total 10 rabbit eyes. Blank liposome or balance salt solution (BSS) was used as control. Slit-lamp examination and histopathological examination was used to evaluated capsule opacifica-tion. Intraocular pressure (IOP) , density and morphology of corneal endothelia cells, the amplitude and latency of b wave of ERG were measured.Results: The inflammatory response was mild both in TAH treated and the control group. PCO formation occurred in the control group 2 weeks postoperatively, but the posterior capsule was clear in TAH treated eyes. 4 weeks and 8 weeks after operation, PCO occurred both in TAH

A Study of Rabbit Lens Epithelial Cells Survival and Growth on the Rabbit Capsular Bag in Vitro

Objective: To study the proliferation, migration and metaplasm of residual rabbit lens epithelial cells (LECs) after extracapsular cataract extraction(ECCE)based on the rabbit capsular bag model in vitro. Methods: Sham cataract surgery, including anterior capsulorhexis, nucleus hydroexpression and aspiration of lens fibers, was performed on 20 rabbit lens. The capsular bags were isolated and pinned to sterile non-toxic silicone rings on petri dishes. The capsular bags were incubated with Eagle's minimum essential medium (DMEM) supplemented with 10% fetal calf serum (FCS) and monitored for 3 weeks by phase-contrast microscopy, after which light microscopy was performed on them.Results: After a latent period of 2-3 d, outgrowth was observed across the posterior capsule. Growth proceeded rapidly so that the posterior capsule was totally covered by a confluent monolayer of cell at 6-8 day. Capsular wrinkles became increasingly apparent as time progressed, causing a marked rise in light scatter. An increase in capsular tension also came.Conclusion: This model exhibits many of the in vito characteristics of the lens capsule after extracapsular surgery and may prove useful in further elucidating the cellular mechanisms of posterior capsule opacification and developing strategies for inhibiting cell growth with this system.

Comparison of design of intraocular lens versus the material for PCO prevention

AIM: To evaluate the influence of different intraocular lens(IOL) designs made of PMMA on posterior capsular opacification(PCO) and compare with foldable designs.· METHODS: Phacoemulsification and IOL implantation was done in one eye of 24 New Zealand White rabbits, with IOL of two different designs (Square edged or round edge) and two different materials(PMMA or HEMA). After three months, the animals were sacrificed and enucleated. Evaluation of PCO included posterior view, migration of anterior capsular epithelial cells to the posterior capsule following epithelial-mesenchymal transition were assessed by staining the histological sections of posterior capsule by hematoxylin-eosin(HE) and Periodic acid- Schiff (PAS). The IOLs were extracted and stained with HE to evaluate the presence of adherent cells on the lens surface. · RESULTS: PCO was highest with round edged rigid lens. There was no significant difference in the PCO between the square edged PMMA and square edged foldable lens.· CONCLUSION: It is the design of the IOL not the material that offers protection on PCO formation.

A new technique for Nd:YAG laser posterior capsulotomy

AIM:To investigate the effects of a new opening pattern in neodymium:yttrium-aluminum-garnet(Nd:YAG)laser posterior capsulotomy on visual function.METHODS:This technique was conducted along a circular pattern.The energy ranged between 0.8 and1.2 mJ/pulse was consumed and mean total energy levels were 74±21 mJ(mean±standard deviation:SD,from 40 to167)and laser shots aimed at 150μm away behind a datum point and went along an imaginary line which extends 0.5 mm inside from optic margin and into the circular en bloc pattern.Vitreous stands were attached with fragment and then they were cut off by the laser after circular application.The circular fragment was completely separated from vitreous,and then this fragment was quickly sunk in intravitreal space.RESULTS:The follow-up period ranges from at least a week to 40mo,making 15.8mo on average.The procedural outcome showed 96%(74 eyes out of the 77eyes)enhancement in patients’visual acuity.Cystoid macular edema or retinal detachment was not observed in any of the patients during follow-up periods.CONCLUSION:This new technique is expected to improve the weaknesses that the conventional procedures have by adding the process to cut off vitreous stands attached with the fragment by the laser to the circular application.

血清及房水IGF-1、SOD水平在预测糖尿病性白内障患者术后发生囊膜混浊中的应用

目的探讨血清及房水胰岛素样生长因子1(IGF-1)、超氧化物岐化酶(SOD)水平在预测糖尿病性白内障(DC)患者术后发生囊膜混浊(PCO)中的应用价值。方法选择120例DC患者为DC组,同期选择接受手术治疗的单纯白内障患者77例为对照组。所有DC患者术后至少随访6个月,根据是否并发PCO将DC患者分为PCO组(21例)和非PCO组(99例)。术前用酶联免疫吸附试验检测血清及房水中IGF-1、SOD,收集DC患者术后发生PCO的相关资料。用多因素Logistic回归分析血清及房水IGF-1、SOD对DC患者术后发生PCO的影响;绘制受试者工作特征(ROC)曲线,用曲线下面积比较血清及房水IGF-1、SOD预测DC患者术后发生PCO的价值。结果DC组血清及房水IGF-1水平高于对照组(P均<0.05),SOD水平低于对照组(P均<0.05)。PCO组年龄、C反应蛋白水平、亲水型人工晶体比例高于非PCO组(P均<0.05)。亲水型人工晶体、房水IGF-1水平高是DC患者术后发生PCO的危险因素(P均<0.05),房水SOD水平高是保护因素(P<0.05)。血清及房水IGF-1、SOD预测DC患者术后发生PCO的曲线下面积分别为0.749、0.720、0.859、0.884,房水IGF-1、SOD预测DC患者术后发生PCO的曲线下面积大于血清IGF-1、SOD预测的曲线下面积(P均<0.05),房水IGF-1、SOD联合预测DC患者术后发生PCO的曲线下面积为0.967,大于房水IGF-1、SOD单独预测的曲线下面积(P均<0.05)。结论房水IGF-1水平升高、SOD水平降低与DC患者术后发生PCO有关,血清及房水中IGF-1、SOD可用于预测DC患者术后PCO的发生,且房水中IGF-1、SOD联合预测的价值较高。

HSYA对人晶状体上皮细胞系SRA01/04生物学特性的影响

目的探讨羟基红花黄色素A(HSYA)对重组人表皮生长因子(rhEGF)诱导的人晶状体上皮细胞系SRA01/04(HLEC-SRA01/04)增殖、迁移及上皮-间质转化(EMT)的影响。方法研究时间为2022年6月至2023年9月。不同浓度HSYA溶液处理rhEGF诱导的HLEC-SRA01/04不同时长,四甲基偶氮唑蓝(MTT)比色法检测各组细胞的增殖状态并计算半数抑制浓度值(IC50)。细胞划痕实验与Transwell小室测定不同浓度组细胞的迁移能力。逆转录荧光定量聚合链式反应法(RT-qPCR)与蛋白印迹法(Western Blot)测定不同浓度组细胞内增殖细胞核抗原(PCNA)及EMT标记物波形蛋白(Vimentin)的mRNA表达水平与蛋白含量。计量资料采用t检验。结果MTT实验结果示:选取20、40、60、80、100μmol/L的HSYA溶液处理5μg/L rhEGF诱导人晶状体上皮细胞24 h后,增殖抑制率分别为(12.1±0.6)%、(19.0±3.8)%、(31.5±2.2)%、(53.7±0.4)%、(70.8±0.3)%,IC50值为(76.520±0.954)μmol/L,48 h增殖抑制率分别为(14.3±3.7)%、(27.4±3.1)%、(42.6±2.7)%、(59.2±2.2)%、(81.0±1.0)%,IC50值为(66.094±2.508)μmol/L,呈明显剂量依赖性。细胞划痕实验结果显示:空白组及0、20、40、70、100μmol/L组的24 h细胞迁移率分别为(46.9±1.8)%、(90.0±1.5)%、(88.4±2.1)%、(43.3±6.6)%、(31.5±16.2)%、(5.82±5.2)%,48 h细胞迁移率分别为(81.1±2.3)%、100%、(95.5±0.1)%、(72.6±3.5)%、(58.5±6.1)%、(37.4±7.1)%。Transwell小室实验结果显示:空白组及0、20、40、70、100μmol/L组的细胞数分别为(171.667±20.407)个、(290.222±24.135)个、(198.667±16.826)个、(161.222±5.981)个、(134.111±6.850)个、(67.444±7.351)个,HSYA对rhEGF诱导人晶状体上皮细胞迁移的抑制呈明显浓度依赖性。RT-qPCR法及Western Blot法结果示:HSYA可明显下调rhEGF诱导的人晶状体上皮细胞内PCNA、Vimentin及mRNA表达水平,呈剂量依赖性。结论HSYA可明显抑制rhEGF诱导的HLEC-SRA01/04增殖、迁移及EMT,可能成为预防后发性白内障的潜在药物。

超声乳化联合玻璃体腔抗VEGF注药术对后发性白内障预防价值分析

目的 分析白内障手术联合玻璃体腔抗血管内皮生长因子(VEGF)治疗对后发性白内障的影响。方法 采用回顾性临床队列研究,回顾性分析2020年1月至2021年3月就诊于苏州大学附属第三医院眼科行白内障手术的患者41例(54眼)。其中,试验组23例(27眼)行白内障超声乳化吸除+人工晶体植入联合玻璃体腔抗VEGF药物注射术;对照组18例(27眼)行单纯白内障超声乳化吸除+人工晶体植入术。所有患者术后随访24个月,比较两组患者术后最佳矫正视力、后发性白内障以及其他眼部并发症的发生情况。结果 术后24个月患者的最佳矫正视力均有不同程度的提高;试验组后发性白内障的发生率明显低于对照组,差异有统计学意义(P <0.05);仅有1例试验组患者出现术后一过性眼压升高,其余患者术后眼压均正常。结论 白内障超声乳化吸除+人工晶体植入联合玻璃体腔抗VEGF药物注射术安全可靠,并可有效降低后发性白内障的发生率。

Drug-eluting intraocular lens with sustained bromfenac release for conquering posterior capsular opacification

Cataract is the leading cause of visual impairment,and posterior capsular opacification(PCO)is the most common long-term complication of modern cataract surgery,which can cause severe visual impairment after surgery.The proliferation,migration,and epithelial-mesenchymal transition(EMT)of residual lens epithelial cells(LECs)stimulated by growth factors and cytokines,are the key pathological mechanisms involved in the development of PCO.This study demonstrated that non-steroidal anti-inflammatory drug(NSAID),bromfenac,was capable of effectively inhibiting cell migration,overexpression of EMT markers,such as fibronectin(FN),matrix metalloproteinase 2(MMP2),α-smooth muscle actin(α-SMA),and transcription factor Snail,and extracellular signal-regulated kinase(ERK)/glycogen synthase kinase-3β(GSK-3β)signaling induced by transforming growth factor-β2(TGF-β2)in vitro.The inhibitory effect of bromfenac on TGF-β2-induced EMT was also verified on a primary lens epithelial cell model using human anterior capsules.Furthermore,based on ultrasonic spray technology,we developed a drug-eluting intraocular lens(IOL)using poly(lactic-co-glycolic acid)(PLGA)with sustained bromfenac release ability for the prevention of PCO development.In the rabbit models of cataract surgery,bromfenac-eluting IOL exhibited remarkable PCO prevention and inflammation suppression effects with excellent biocompatibility.In conclusion,bromfenac can inhibit TGF-β2-induced cell migration and the EMT of LECs via ERK/GSK-3β/Snail signaling.The present study offers a novel approach for preventing PCO through PLGA-based drug sustained-release IOLs.

Augmented cellular uptake and homologous targeting of exosome-based drug loaded IOL for posterior capsular opacification prevention and biosafety improvement

Posterior capsular opacification(PCO),the most common complication after cataract surgery,is caused by the proliferation,migration and differentiation of residual lens epithelial cells(LECs)on the surface of the intraocular lens(IOL).Although drug-loaded IOLs have been successfully developed,the PCO prevention efficacy is still limited due to the lack of targeting and low bioavailability.In this investigation,an exosome-functionalized drug-loaded IOL was successfully developed for effective PCO prevention utilizing the homologous targeting and high biocompatibility of exosome.The exosomes derived from LECs were collected to load the anti-proliferative drug doxorubicin(Dox)through electroporation and then immobilized on the aminated IOLs surface through electrostatic interaction.In vitro experiments showed that significantly improved cellular uptake of Dox@Exos by LECs was achieved due to the targeting ability of exosome,compared with free Dox,thus resulting in superior anti-proliferation effect.In vivo animal investigations indicated that Dox@Exos-IOLs effectively inhibited the development of PCO and showed excellent intraocular biocompatibility.We believe that this work will provide a targeting strategy for PCO prevention through exosome-functionalized IOL.

Consilience and unity in ocular anterior segment research

In his beautiful book,Consilience:The Unity of Knowledge,the eminent biologist Edward O Wilson,advocates the need for integration and reconciliation across the sciences.He defines consilience as“literally a‘jumping together’of knowledge with a linking of facts…to create a common groundwork of explanation”.It is the premise of this paper that as much as basic biomedical research is in need of data generation using the latest available techniques–unifying available knowledge is just as critical.This involves the necessity to resolve contradictory findings,reduce silos,and acknowledge complexity.We take the cornea and the lens as case studies of our premise.Specifically,in this perspective,we discuss the conflicting and fragmented information on protein aggregation,oxidative damage,and fibrosis.These are fields of study that are integrally tied to anterior segment research.Our goal is to highlight the vital need for Wilson’s consilience and unity of knowledge which in turn should lead to enhanced rigor and reproducibility,and most importantly,to greater understanding and not simply knowing.

Overexpression of TRPV1 activates autophagy in human lens epithelial cells under hyperosmotic stress through Ca^(2+)-dependent AMPK/mTOR pathway

●AIM:To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells(LECs)under hyperosmotic stress.●METHODS:LECs were treated with hyperosmotic stress at the concentration of 270,300,400,500,or 600 mOsm for 6,12,18,24h in vitro.Polymerase chain reaction(PCR)was employed for the mRNA expression of autophagyrelated genes,while Western blotting detected the targeted protein expression.The transfection of stub-RFP-sens-GFPLC3 autophagy-related double fluorescence lentivirus was conducted to detect the level of autophagy flux.Scanning electron microscopy was used to detect the existence of autolysosome.Short interfering RNA of autophagy-related gene(ATG)7,transient receptor potential vanilloid(TRPV)1 overexpression plasmid,related agonists and inhibitors were employed to their influence on autophagy related pathway.Flow cytometry was employed to test the apoptosis and intracellular Ca^(2+)level.Mitochondrial membrane potential was measured by JC-1 staining.The cell counting kit-8 assay was used to calculate the cellular viability.The wound healing assay was used to evaluate the wound closure rate.GraphPad 6.0 software was utilized to evaluate the data.●RESULTS:The hyperosmotic stress activated autophagy in a pressure-and time-dependent manner in LECs.Beclin 1 protein expression and conversion of LC3B II to LC3B I increased,whereas sequestosome-1(SQSTM1)protein expression decreased.Transient Ca^(2+)influx was stimulated caused by hyperosmotic stress,levels of mammalian target of rapamycin(mTOR)phosphorylation decreased,and the level of AMP-activated protein kinase(AMPK)phosphorylation increased in the early stage.Based on this evidence,autophagy activation through the Ca^(2+)-dependent AMPK/mTOR pathway might represent an adaptation process in LECs under hyperosmotic stress.Hyperosmotic stress decreased cellular viability and accelerated apoptosis in LECs and cellular migration decreased.Inhibition of autophagy by ATG7 knockdown had similar results.TRPV1 overexpression increased autophagy and might be crucial in the occurrence of autophagy promoted by hyperosmotic stress.●CONCLUSION:A combination of hyperosmotic stress and autophagy inhibition may be a promising approach to decrease the number of LECs in the capsular bag and pave the way for improving prevention of posterior capsular opacification and capsular fibrosis.

Fabrication of a 3D bioprinting model for posterior capsule opacification using GelMA and PLMA hydrogel-coated resin

Posterior capsule opacification(PCO)remains the predominant complication following cataract surgery,significantly impairing visual function restoration.In this study,we developed a PCO model that closely mimics the anatomical structure of the crystalline lens capsule post-surgery.The model incorporated a threaded structure for accurate positioning and observation,allowing for opening and closing.Utilizing 3D printing technology,a stable external support system was created using resin material consisting of a rigid,hollow base and cover.To replicate the lens capsule structure,a thin hydrogel coating was applied to the resin scaffold.The biocompatibility and impact on cellular functionality of various hydrogel compositions were assessed through an array of staining techniques,including calcein-AM/PI staining,rhodamine staining,BODIPY-C11 staining and EdU staining in conjunction with transwell assays.Additionally,the PCO model was utilized to investigate the effects of eight drugs with anti-inflammatory and anti-proliferative properties,including 5-aminoimidazole-4-carboxamide ribonucleotide(AICAR),THZ1,sorbinil,4-octyl itaconate(4-OI),xanthohumol,zebularine,rapamycin and caffeic acid phenethyl ester,on human lens epithelial cells(HLECs).Confocal microscopy facilitated comprehensive imaging of the PCO model.The results demonstrated that the GelMA 605%þPLMA 2%composite hydrogel exhibited superior biocompatibility and minimal lipid peroxidation levels among the tested hydrogels.Moreover,compared to using hydrogel as the material for 3D printing the entire model,applying surface hydrogel spin coating with parameters of 2000 rpm�2 on the resin-based 3D printed base yielded a more uniform cell distribution and reduced apoptosis.Furthermore,rapamycin,4-OI and AICAR demonstrated potent antiproliferative effects in the drug intervention study.Confocal microscopy imaging revealed a uniform distribution of HLECs along the anatomical structure of the crystalline lens capsule within the PCO model,showcasing robust cell viability and regular morphology.In conclusion,the PCO model provides a valuable experimental platform for studying PCO pathogenesis and exploring potential therapeutic interventions.

后发性白内障患者行Nd∶YAG激光术后视觉质量

目的:探究角膜/屈光分析仪OPD-Scan Ⅲ评估后发性白内障患者行Nd∶YAG激光术后视觉质量。方法:回顾性研究。选取2021-05/2023-04于我院行Nd∶YAG激光后囊膜切开术治疗的后发性白内障患者98例98眼,采用角膜/屈光分析仪OPD-Scan Ⅲ获取患者高阶像差参数(彗差、球差和三叶草像差)和视觉质量参数[斯特列尔比(SR)和人眼调制传递函数(MTF)曲线中4 mm面积比(AR)],比较患者术前,术后1 wk,3 mo时视力、高阶像差和视觉质量。结果:纳入患者手术前后裸眼远视力(UDVA)、裸眼中视力(UIVA)、裸眼近视力(UNVA)、彗差、球差、三叶草、SR和AR比较均有差异(均P<0.001)。术后1 wk,3 mo UDVA、UIVA、UNVA、彗差、球差、三叶草、SR和AR与术前比较均有差异(均P<0.05)。术后3 mo UDVA、UIVA、UNVA、SR和AR与术后1 wk比较均有差异(均P<0.05),术后3 mo彗差、球差、三叶草与术后1 wk比较均无差异(均P>0.05),术后3 mo球差、三叶草与SR均呈负相关(r_(s)=-0.427,P=0.009;r_(s)=-0.436,P=0.010),三叶草与AR呈负相关(r_(s)=-0.406,P=0.015)。结论:后发性白内障患者Nd∶YAG激光术后视力改善,使用角膜/屈光分析仪OPD-Scan Ⅲ系统反映患者视觉质量具有较高的临床价值。

基于网络药理学和分子对接技术探讨金钗石斛生物碱抗后发性白内障的作用机制

目的:探讨金钗石斛生物碱抗后发性白内障的作用机制。方法:通过查阅国内外文献,收集金钗石斛生物碱类活性成分及其结构,利用网络药理学预测金钗石斛生物碱抗后发性白内障的潜在靶点,建立金钗石斛生物碱抗后发性白内障的蛋白互作关系网络(PPI),并对潜在靶点进行GO分析和KEGG通路富集分析,探索金钗石斛防治后发性白内障可能的生物进程及通路。通过分子对接验证金钗石斛生物碱与核心靶点的结合活性。结果:网络药理学分析表明,获得金钗石斛生物碱类活性成分27个,金钗石斛生物碱抗后发性白内障的核心靶点为STAT3、PIK3R1、AKT1等,GO富集分析结果表明,金钗石斛生物碱主要通过影响细胞凋亡、细胞迁移和激酶活性的双向调节等生物进程,发挥酶结合和蛋白质结合等分子结合,进而发挥抗后发性白内障的作用。金钗石斛抗后发性白内障可能与血管生成(HIF-1信号通路)、炎症反应(PI3K-Akt信号通路)等信号通路有关。分子对接结果显示金钗石斛生物碱与核心靶点均有较好的结合活性。结论:金钗石斛中石斛碱(dendrobine)、N-反式阿魏酸酰对羟基苯乙胺(N-trans-feruloyl tyramine)可能是通过STAT3、PIK3R1、AKT1等多靶点、多信号通路、多途径发挥对后发性白内障的防治作用,为后期的实验验证及金钗石斛药材的开发提供理论指导。

糖尿病兔晶状体后囊膜混浊模型的建立

背景实验性糖尿病动物模型的制作是对糖尿病性眼病进行实验研究的关键环节，目前国内普遍应用的方法是链脲佐菌素和四氧嘧啶（ALX）注射，但前者价格昂贵，后者造模过程中动物的死亡率较高。目的探讨ALX注射制作糖尿病兔晶状体后囊膜混浊（PCO）模型并降低死亡率的方法，并观察高血糖对晶状体PCO形成的早期影响。方法将清洁级健康新西兰雄性大白兔40只随机分为2组；其中20只兔经耳缘静脉一次性注射ALX90mg／kg建立糖尿病模型作为高血糖组，另20只兔以同样的方法注射等量生理盐水作为正常血糖组。药物注射后2周时高血糖组兔血糖升高到12．0mmol／L以上可判断为建模成功，2组分别行兔右眼透明晶状体囊外摘出术并对晶状体PCO进行分级。于术后第6、10、14天取眼球，应用免疫组织化学法观察增生细胞核抗原（PCNA）在后囊膜晶状体上皮细胞（LECs）中的表达情况。结果ALX注射后糖尿病兔的成模率为70％。术后第6、10、14天时，高血糖组兔体质量均明显低于正常血糖组，但血糖明显高于正常血糖组，差异均有统计学意义（P〈0．05）。高血糖组术后14d时观察的3只兔中，2只兔出现后囊膜2级混浊，另1只兔出现1级混浊。正常血糖组术后14d时观察的3只兔后囊膜均出现1级混浊。免疫组织化学染色显示，术后第10天高血糖组可见PCNA在LECs的细胞核中表达，但正常血糖组未见PCNA的表达。术后第14天时高血糖组PCNA增生指数为0．86±0．04，明显高于正常血糖组的0．25±0．03，差异有统计学意义（t=-16．171，P=0．000）。结论90mg／kg的ALX静脉注射能形成稳定的糖尿病兔PCO模型；高血糖是促进PCO发生发展的重要因素之一。

预防儿童后发性白内障3种不同术式的临床探讨

目的 探讨儿童白内障术中 3种不同后囊处理方法对后发性白内障的预防作用。方法 4 2例 (5 1眼 )白内障儿童 ,年龄 2～ 14岁 ,在白内障联合人工晶状体植入术中 ,分别采用 3种不同后囊处理方法 :Ⅰ组行大面积后囊抛光 ,保留完整后囊 ;Ⅱ组行后囊连续环形撕囊 ;Ⅲ组行连续环形撕囊联合前段玻璃体切割术。随访 2个月～ 3a,对术后视力、后囊混浊情况及并发症进行分析。结果 3级以上后囊混浊Ⅰ组为71% ,Ⅱ组为 2 4 % ,Ⅲ组为 0 % .各组均无视网膜脱离、黄斑水肿等并发症出现。结论 儿童白内障摘出联合人工晶状体植入术中I期后囊环形撕囊 ,一定程度上减少后囊混浊的发生 ;后囊环形撕囊联合前部玻璃体切割术可有效地预防儿童后发性白内障的发生 ,其远期效果及并发症有待进一步观察和研究。

骆驼蓬总碱及其脂质体对兔晶状体上皮细胞的抑制作用

目的探讨骆驼蓬总碱（ＴＡＨ）及其脂质体（ＬＴＡＨ）对兔后囊混浊（ＰＣＯ）形成的影响。方法用改良冻融法制备ＬＴＡＨ。１０只健康纯种新西兰白兔分别每眼行晶状体囊外摘出术并分别注入０１ｍｌ浓度为０２ｍｇ／ｍｌＴＡＨ及ＬＴＡＨ。观察术后后囊、手术前后眼压、角膜内皮细胞、视网膜电图及组织病理学变化。结果注药术后４周实验眼与对照眼角膜内皮细胞密度及形态、视网膜电图的ｂ波振幅及潜时无明显差别。组织病理学检查显示对照组眼明显残留晶状体上皮细胞（ＬＥＣ）增生并有Ｓｏｅｍｍｅｒｉｎｇ环形成，而用药眼无明显的残留ＬＥＣ增殖且细胞空泡变性。结论ＴＡＨ及ＬＴＡＨ能抑制兔眼残留ＬＥＣ增殖，有可能成为一种预防后发性白内障的药物。