Nomogram for predicting non-proliferative vitreoretinopathy probability after vitrectomy in eyes with rhegmatogenous retinal detachment

AIM:To identify the risk factors for postoperative proliferative vitreoretinopathy(PVR)in patients with primary rhegmatogenous retinal detachment(RRD)and develop a nomogram for predicting postoperative PVR-free probability.METHODS:A total of 741 patients(741 eyes)diagnosed with primary RRD who underwent first surgery in the same hospital were retrospectively reviewed and randomly assigned with 521 to the training set and 220 to the validation set.Univariate and multivariate logistic regression analyses were performed in the training cohort to determine risk factors to construct a nomogram for predicting the 3-,4-,5-,and 6-month postoperative PVR-free probabilities.Nomogram performance was estimated by the concordance index(C-index),calibration plot,and the area receiver operating characteristic(ROC)curve.RESULTS:A nomogram was constructed based on the preoperative PVR,silicone oil tamponade time(SOTT),photocoagulation energy(PE),retinal tear size(RTS),and hypertension.In the training set,the C-index of the nomogram was 0.896,0.936,0.961,and 0.972 at 3,4,5,and 6mo,respectively.The C-index values in the validation set were 0.860,0.936,0.951,and 0.965 at 3,4,5,and 6mo,respectively.Decision-curve analysis indicated that only the 4-,5-,and 6-month nomograms had significant net benefits over a large threshold probabilities interval.CONCLUSION:Preoperative PVR,SOTT,PE,RTS,and hypertension are significant risk factors for postoperative PVR formation in patients with primary RRD.The proposed nomogram can effectively predict the 4-,5-,and 6-month PVR-free probabilities after surgery and assist in making clinical decisions during follow-up.

Intravitreal slow-release dexamethasone alleviates traumatic proliferative vitreoretinopathy by inhibiting persistent inflammation and Müller cell gliosis in rabbits

AIM:To evaluate the effects of intravitreal slow-release dexamethasone on traumatic proliferative vitreoretinopathy(PVR)and Müller cell gliosis and preliminarily explored the possible inflammatory mechanism in a rabbit model induced by penetrating ocular trauma.METHODS:Traumatic PVR was induced in the right eyes of pigmented rabbits by performing an 8-mm circumferential scleral incision placed 2.5 mm behind the limbus,followed by treatment with a slow-release dexamethasone implant(Ozurdex)or sham injection.Left eyes were used as normal controls.The intraocular pressure(IOP)was monitored using an iCare tonometer.PVR severity was evaluated via anatomical and histopathological examinations every week for 6wk;specific inflammatory cytokine and proliferative marker levels were measured by quantitative real-time polymerase chain reaction,Western blot,protein chip analysis,or immunofluorescence staining.RESULTS:During the observation period,PVR severity gradually increased.Intense Müller cell gliosis was observed in the peripheral retina near the wound and in the whole retina of PVR group.Ozurdex significantly alleviated PVR development and Müller cell gliosis.Post-traumatic inflammation fluctuated and was persistent.The interleukin-1β(IL-1β)mRNA level was significantly upregulated,peaking on day 3 and increasing again on day 21 after injury.The expression of nod-like receptor family pyrin domain containing 3(NLRP3)showed a similar trend that began earlier than that of IL-1βexpression.Ozurdex suppressed the expression of IL-1β,NLRP3,and phosphorylated nuclear factor-kappa B(NF-κB).The average IOP after treatment was within normal limits.CONCLUSION:The present study demonstrates chronic and fluctuating inflammation in a traumatic PVR rabbit model over 6wk.Ozurdex treatment significantly inhibites inflammatory cytokines expression and Müller cell gliosis,and thus alleviates PVR severity.This study highlights the important role of IL-1β,and Ozurdex inhibites inflammation presumably via the NF-κB/NLRP3/IL-1βinflammatory axis.In summary,Ozurdex provides a potential therapeutic option for traumatic PVR.

Effect of etanercept on post-traumatic proliferative vitreoretinopathy

AIM: To evaluate the safety and efficacy of intravitreal etanercept in the inhibiting of proliferative vitreoretinopathy(PVR) in a model of penetrating ocular injury. METHODS: Penetrating ocular injury on the retina of rabbit was induced, which was subsequently treated using 0.1 mL of sterile water or 0.1 m L of 12.5 mg/mL etanercept. The development of PVR was evaluated by fundus images, the B-scan, and the histopathology. The mRNA and protein expressions of tumor necrosis factor-α(TNF-α), transforming growth factor β(TGF-β) as well as connective tissue growth factor(CTGF) were examined at various time points after the etanercept injection with the reverse transcriptase-polymerase chain reaction(RT-PCR) and Western blotting, respectively. The safety of etanercept was evaluated by injection of 12.5 mg/mL etanercept into a normal rabbit eye without penetrating trauma. RESULTS: Clinical assessment and grading clearly demonstrated that the PVR formation was prevented in etanercept-treated animals, which was confirmed via fundus images, B-scan and histopathology. The RT-PCR and Western blotting showed increased mRNA and protein expression of TNF-α, TGF-β as well as CTGF in the retina of rabbits following penetrating ocular injury, and these factors were dramatically mitigated by ocular etanercept treatment. In addition, there was no adverse effect of etanercept intravitreal injection in normal eyes without penetrating trauma, it showed normal structure and histology. CONCLUSION: The etanercept is a potential therapy for inhibiting PVR development. To assess the clinic application of the etanercept in preventing PVR, further clinical studies are required.

Expression of IGFBP-6 in a proliferative vitreoretinopathy rat model and its effects on retinal pigment epithelial cell proliferation and migration

AIM: To investigate the expression of insulin-like growth factor binding protein-6(IGFBP-6) in a proliferative vitreoretinopathy(PVR) model and its effects on proliferation and migration in retinal pigment epithelial(RPE) cells. ·METHODS: A PVR Wistar rat model was established by the intravitreal injection of RPE-J cells combined with platelet-rich plasma(PRP). The expression levels of IGFBP-6 were tested by ELISA. ARPE-19 cell proliferation was evaluated by the MTS method,and cell migration was evaluated by wound healing assays. ·RESULTS: The success rate of the PVR model was 89.3%(25/28). IGFBP-6 was expressed at higher levels in the vitreous,serum and retina of rats experiencing advanced PVR(grade 3) than in the control group(vitreous: 152.80 ±15.08ng/mL vs 105.44 ±24.81ng/mL,P 】 0.05; serum: 93.48 ±9.27ng/mL vs 80.59 ±5.20ng/mL,P 【 0.05; retina: 3.02±0.38ng/mg vs 2.05±0.53ng/mg,P 【0.05). In vitro,IGFBP-6(500ng/mL) inhibited the IGF-II(50ng/mL) induced ARPE-19 cell proliferation(OD value at 24h: from 1.38±0.05 to 1.30±0.02; 48h: from 1.44±0.06 to 1.35± 0.05). However,it did not affect basal or VEGF-,TGF-β-and PDGF-induced cell proliferation. IGFBP-6(500ng/ml) reduced the IGF-II(50ng/mL)-induced would healing rate [24h: from(43.91 ±3.85)% to(29.76 ±2.49)%; 48h: from(66.09±1.67)% to(59.88±3.43)%]. ·CONCLUSION: Concentrations of IGFBP-6 increased in the vitreous,serum,and retinas only in advanced PVR in vivo. IGFBP-6 also inhibited IGF-II-induced cell proliferation in a not dose or time dependent manner and migration. IGFBP-6 participates in the development of PVR and might play a protective role in PVR.

Outcomes and predictors of vitrectomy and silicone oil tamponade in retinal detachments complicated by proliferative vitreoretinopathy

AIM:To evaluate outcomes and determine factors influencing the outcomes of vitrectomy with silicone oil(SO)endotamponade for the management of rhegmatogenous retinal detachment(RRD)complicated by advanced proliferative vitreoretinopathy(PVR).METHODS:This is a retrospective,interventional case series of eyes with PVR grade C associated RRD with or without prior surgery that underwent vitreoretinal surgery and SO tamponade.Eyes with a minimum follow-up of 6mo after SO extraction were included.Eyes were classified into three PVR subgroups according to severity and extension of proliferation.The influence of several preoperative,intraoperative and postoperative factors upon the functional and anatomical outcomes was assessed using multivariate logistic regression analysis.RESULTS:A hundred and one eyes of 101 patients that met the inclusion criteria were studied.Seventy-five of 101 eyes(74.3%)had successful retinal reattachment after one operation.Increased aqueous cell and flare at the first week exam had a statistically significant association with redetachment,recurrent membrane proliferation and keratopathy.Visual acuity improvement was significantly associated with faint postoperative aqueous inflammation values,primary vitrectomy and PVR outside of the posterior pole.CONCLUSION:Although encouraging anatomical and functional outcomes are achieved after vitrectomy and SO tamponade in eyes with RRD complicated by PVR,an increase in aqueous flare or cells at the first week follow-up is most likely to result in postoperative late complications.Primary vitrectomy,PVR associated with minimal posterior pole extension and absent to mild postoperative aqueous inflammation are associated with improved post-operative final visual acuity.

Evaluating for Vitreous Surgery Used in Proliferative Vitreoretinopathy Grede D_3

Proliferative vitreoretinopathy (PVR) is one of the main failure causes of retinal detachment repair. In this paper, 25 cases of vitreous surgery used in the PVR D3 are analyzed. The diagnosis of PVR depended on the classification of the America Retina Society Terminology Committee. Vitrectomy and peeling were carried out in all of the patients. Intraocular tamponade included silicone oil and gas tamponade. Follow-up is more than 3 months. The anatomic successful rate was 68% and 11 cases arrived 20/400...

Anterior proliferative vitreoretinopathy in a patient with Coats disease

Dear Editor,I am Satoru Kase,from the Department of Ophthalmology,Faculty of Medicine and Graduate School of Medicine,Hokkaido University,Sapporo,Japan.I write to present a case of Coats disease showing anterior proliferative vitreoretinopathy（PVR）and neovascular glaucoma.

Upregulation of ASPP2 expression alleviates the development of proliferative vitreoretinopathy in a rat model

AIM:To investigate whether upregulation of apoptosisstimulating p53 protein 2(ASPP2)expression could alleviate the development of proliferative vitreoretinopathy(PVR)in a rat model.METHODS:ASPP2-lentivirus or scrambled-lentivirus were transfected into ARPE-19 cells,followed with measurements of cell cytotoxicity by cell counting kit-8 assay.ASPP2 upregulation was confirmed by Western blotting and immunocytochemistry.Then ARPE-19 cells pretreated with ASPP2-lentivirus were intravitreally injected to Brown Norway rats to induce PVR models.PVR development and retinal function were evaluated by retinal photography and electroretinography,respectively.Finally,epithelial-mesenchymal transition as well as autophagy were investigated in rats’retinas via Western blotting.RESULTS:Protein expression of ASPP2 was significantly upregulated by ASPP2-lentivirus transfection in ARPE-19 cells.The development and progression of PVR were impeded significantly in rats with intravitreal injection of ARPE-19 cells pretreated with ASPP2-lentivirus.Accordingly,retinal functions were less affected and PVR grades were much lower in rats with ASPP2-lentivirus compared to scrambledlentivirus treatment.Moreover,epithelial-mesenchymal transition and autophagy markers were decreased in the retinas of rats treated with ASPP2-lentivirus.CONCLUSION:ASPP2-lentivirus transfected to ARPE-19 cells mitigates the progression of PVR in rat models,which might be partly through reduced autophagy and attenuated epithelial-mesenchymal transition.ASPP2 might stand as a new approach for PVR treatment in the future.

Quantitative Study of Basic Fibroblast Growth Factor in Vitreous with Proliferative Vitreoretinopathy

Objective:To quantitatively study basic fibroblast growth factor(bFGF)in the vitreous ofproliferative vitreoretionopathy(PVR)inorder to understand the role of bFGFin the develop-ment of PVR.Method:High sensitive sandwich enzyme immunoassay technique(ELISA)was used to measure bFGF level in vitreous of normal eyes,the eyes of PVR-Cor pVR-Dgrade,eyes of vitreous hemorrhage and the serum levels of bFGF in PVR-Dpatients.Results:The levels of bFGF in the vitreous were:median5.20ng/L,quartile15.47ng/Lin20normal eyes;median3.12ng/L,quartile10.48ng/Lin35PVR-Ceyes;median46.56ng/L,quartile113.96ng/Lin26pPVR-Deyes;median1.40ng/L,quar-tile6.25ng/Lin25vitreous hemorrhage eyes.The vitreous bFGF level in PVR-D group was significantly higher than that in the normal group,PVR-Cgroup and vitreous hemorrhage group(P<0.01).The mean of serum-bFGFlevel was18.33±3.39ng/L.The vitreous bFGFlevel ofPVR-Dgroup was significantly higher than serum-bFGFlev-el(P<0.01).And the vitreous-bFGFlevel in PVR-Dgroup was significantly higher in larger retinal tear subgroup.Conclusion:The results suggested that bFGF is involved in the development of PVR.Eye Science2000;16:7-10.

散血明目片抑制积血所致PVR的实验研究

目的 :研究散血明目片对兔玻璃体积血所致PVR的影响。方法 :采用自体血造兔右眼玻璃体积血模型 ,分别于造模后 4周、8周观察增殖膜分级 ,采用酶联免疫双抗体夹心法 (ELISA)检测积血玻璃体中TNF α、IL 6含量。结果 :玻璃体积血 4周 ,玻璃体内增殖不明显 ;TNF α、IL 6含量 :散血明目片治疗组与血塞通对照组之间有显著性差异 (P <0 .0 5 ) ,与模型组之间TNF α有显著性差异 (P <0 .0 1)、IL 6无显著性差异 (P >0 .0 5 ) ,与空白组有显著性差异 (P <0 .0 5 ) ,维持了TNF α、IL 6的高表达 ;8周 ,散血明目片组增殖最轻 ;TNF α、IL 6含量明显降到低水平 ,与血塞通对照组有显著性差异 (P <0 .0 5或P <0 .0 1) ,与模型组之间有显著性差异 (P <0 .0 1) ,与空白组无显著性差异 (P >0 .0 5 )。结论 :散血明目片在玻璃体积血的早期能维持玻璃体内TNF α、IL 6的高表达 ,在积血的中晚期能够降低玻璃体内的TNF α、IL 6的含量。因此 ,散血明目片不仅可以加速玻璃体积血的清除 ,并且可以抑制玻璃体内细胞增生的启动、细胞的移行和增殖 ,从而预防PVR的发生发展。

活血利水法对兔外伤性PVR增殖膜上EGFmRNA表达的影响

目的:探讨活血利水之散血明目片对外伤性增生性玻璃体视网膜病变(traumatic proliferrative vitreoretinopathy,tPVR)增殖膜(epiretinal membrane,ERM)中EGFmRNA表达的影响及防治PVR的作用机制。方法:将40只成年有色家兔随机抽取32只,制作tPVR模型,随机分成模型组(B组)、活血利水组(C组)、活血化瘀(D组)、利水明目组(E组),另8只为空白组(A组)。连续灌胃30d后,观察眼底PVR分级情况,原位杂交法检测EGFmRNA在各组的表达,HE染色观察病理组织学改变。结果:给药7d后,B,D,E组PVR分级比较,差异无统计学意义(P>0.05),给药30d后,C组与各组比较,差异有统计学意义(P<0.05);在C组,ERM中EGFmRNA阳性程度低于B组,差异有显著统计学意义(P<0.01)。D组与E组也能降低EGFmRNA表达的阳性程度,与B组相比有统计学差异(P<0.05)。C组中EGFmRNA阳性程度低于另两个治疗组,有统计学差异(P<0.05)。C组中EGFmRNA阳性程度略高于A组,有统计学差异(P<0.01)。结论:活血利水法是活血化瘀和利水明目两者作用的协同,能通过拮抗ERM中EGFmRNA表达的作用来抑制增殖细胞的过度增生,从而防治PVR形成和发展。

选择性PDGF受体酪氨酸激酶抑制剂对兔PVR的治疗作用

目的 评价一种新的血小板源性生长因子 (platelet derivedgrowthfactor,PDGF)受体酪氨酸激酶抑制剂AG12 95对兔增殖性玻璃体视网膜病变 (proliferativevitreoretinopathy ,PVR)的治疗作用。 方法 兔结膜成纤维细胞 (rabbitconjunctivalfibroblastscells,RCF)培养 ,用MTT分析法检测PDGF AA和 BB以及AG12 95对兔RCF的增殖状况的影响。建立PVR动物模型 ,玻璃体腔内给予AG12 95 ,用牵引性视网膜脱离 (tractionalretinaldetach ment,TRD)的发生率判断药物的体内疗效。眼视网膜电生理检查和HE染色分析药物的毒性。结果 10 μmol·L-1和 10 0 μmol·L-1两种浓度的AG12 95均可显著抑制由PDGF AA和 BB诱导的成纤维细胞的增生 ,10 0 μmol·L-1AG12 95可减缓兔TRD的发生 ,但其作用仅持续至第 2 1d。在AG12 95治疗组中 ,未发现明显的网膜毒性。结论 PDGF受体酪氨酸激酶抑制剂AG12 95可减缓兔TRD的发生。

外伤性aPVR引起慢性低眼压的发病机制探讨

目的 探讨外伤性前部增生性玻璃体视网膜病变 (aPVR)病理状态下低眼压的发生、发展及转归 ,为防治外伤性aPVR引起的慢性低眼压提供理论依据。方法 利用青紫兰兔制作外伤性aPVR引起慢性低眼压的动物模型 (n =8) ,于术前及术后不同时间点分别观测眼压 (IOP) ,并行光镜及电镜观察。结果 术后 1周、2周、4周、8周实验组平均眼压明显低于对照组(P <0 0 1)。光镜检查发现实验组术后 2周、4周、8周睫状体水肿 ,术后 4周及 8周睫状体无色素上皮萎缩、缺失。电镜检查发现实验组术后 4周和 8周睫状体无色素上皮线粒体明显减少 ,细胞内空泡。结论 外伤性aPVR睫状膜的增生和收缩引起对睫状上皮的牵拉 ,造成睫状体无色素上皮萎缩和睫状体水肿 ,进而促进慢性低眼压的发生。

MyD88依赖性NF-κB信号途径改变对家兔PVR模型玻璃体内TNF-α变化的影响

目的以有色家兔为实验动物制作兔眼PVR模型,并向眼内转染腺病毒携带的无功能-MyD88（Dn-MyD88）,通过阻断核转录因子-κB（nuclear factor kappa B,NF-κB）信号通路而观察增生性玻璃体视网膜病变（proliferative vitreoretinopathy,PVR）中肿瘤坏死因子-α（tumor necrosis facturα,TNF-α）含量的变化。方法制备含血小板浓度为（50~100）×109L的血浆,制作兔眼PVR模型,向兔眼玻璃体内转染腺病毒携带的Dn-MyD88,运用Western blotting检测向玻璃体内转染腺病毒携带的无功能MyD88成功,并于注射后第1天、第7天、第14天、第21天和第28天分别处死动物,在液氮低温条件下,取得玻璃体样本,对玻璃体液行酶联免疫双抗夹心法（ELISA）检测玻璃体中TNF-α含量。结果空白对照组各时间点玻璃体中TNF-α的含量并无明显变化,PVR注射生理盐水组各时间点玻璃体中TNF-α的含量随着时间的推移呈上升趋势,在造模后第28天时达到最高,为（1073.74±190.43）ng.L-1,PVR注射腺病毒携带的Dn-MyD88组各时间点玻璃体中TNF-α含量呈缓慢上升趋势,在造模后第28天时TNF-α的含量为（612.47±59.29）ng.L-1,与PVR注射生理盐水组相比,差异有统计学意义（P〈0.05）。结论在兔眼PVR模型中通过转染腺病毒携带的Dn-MyD88阻断MyD88依赖性NF-κB信号传导通路而抑制PVR的发生发展,可为PVR的治疗提供新的方法。[眼科新进展2010;30（10）：933-936]

活血利水法对外伤性PVR兔眼玻璃体FNmRNA表达的影响

目的:探讨活血利水法对外伤性增生性玻璃体视网膜病变(proliferative vitreoretinopathy,PVR)纤维连接蛋白信使核糖核酸(FNmRNA)的影响。方法:用兔眼后节穿通伤加注入血浆法制备PVR模型,利用免疫组化法对正常组、模型组、活血利水组、活血化瘀组、利水明目组PVR中的玻璃体腔增殖膜FNmRNA进行检测。结果:活血利水组增殖膜中FNmRNA的阳性表达低于模型组、活血化瘀组和利水明目组(P<0.05)。结论:活血利水法能够降低PVR增殖膜中FNmRNA的阳性表达,抑制PVR的发生发展。

NLRP3炎症小体信号通路在视网膜疾病发生发展中的作用

核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎症小体是由多种蛋白组成的炎症复合物,其主要作用是参与炎症反应。当上述小体激活后可进一步激活Caspase-1,从而诱导一系列炎性因子激活及细胞焦亡。炎性小体的过度活化会引起炎性因子的过量表达,并持续发挥效应,触发免疫失调及炎性连锁反应,造成严重的损害。研究证实糖尿病视网膜病变(DR)、视网膜缺血-再灌注损伤(RIRI)、增生性玻璃体视网膜病变(PVR)等视网膜疾病与免疫失调与炎性反应密切相关,是引起视网膜疾病进展的重要因素。文章就NLRP3炎症小体信号通路及其在视网膜疾病中的功能作一概述,为该病的发病机制及防治提供新思路。

汉防己甲素联合5-FU聚乳酸微球对兔PVR IL-1β和TNF-α表达的影响

目的:探讨汉防己甲素(tetrandrine,Tet)联合5-FU聚乳酸微球对兔增生性玻璃体视网膜病变(proliferati vevitreoretinopathy,PVR)IL-1β和TNF-α表达的影响。方法:随机分为A,B,C3组,建立兔眼外伤性PVR模型,向玻璃体中后部注入药物,A组注入含有Tet联合5-氟尿嘧啶(5-FU)聚乳酸微球的BSS悬浮液0.2mL,B组注入含有5-FU聚乳酸微球的BSS悬浮液0.2mL,C组注入25mg无药物聚乳酸微球的BSS悬浮液0.2mL,术后每天观察眼底变化,必要时行B超检查直到注药后第28d。分别于术后7,14,28d等3个时间点抽取各术眼玻璃体液0.2mL,酶联免疫吸附法(ELISA)检测玻璃体液中TNF-α,IL-2的含量。结果:Tet联合5-FU聚乳酸微球组与5-FU聚乳酸微球组及空白微球组相比,其玻璃体液中TNF-α,IL-2等炎性因子的含量也显著低于其他两组,方差分析P<0.01,差异有统计学意义。结论:Tet在眼内能够降低炎性因子TNF-α和IL-1β的表达,说明Tet可能通过在PVR炎症期发挥抗炎作用,抑制眼内炎症因子的释放,减弱炎症因子对炎性细胞的激活和趋化,从而起到降低PVR发生率的协同作用。

PVR增生膜内核因子与炎性细胞因子关系初步探讨

目的 观察炎前因子mRNA和核因子κB(nucleartranscriptionfactor κB ,NF κB)在增生性玻璃体视网膜病变 (PVR)增生膜中的表达情况。以探讨 2者间可能存在的关系 ,进一步研究PVR的发病机理。方法 收集 16例PVR增生膜 ,石蜡包埋切片 ,免疫组化染色观察NF κB表达 ,原位杂交法观察炎前因子mRNA的表达 ,同时对 5例角膜移植后的供体眼视网膜进行观察。结果 正常人视网膜NF κB在内外核层弱表达 ,未检测到炎前因子mRNA的表达。 16例增生膜有 5例NF κB表达 ,均为C级膜 ,阳性表达的NF κB表达位于胞核中。 6例样本有炎性因子基因表达 ,C级膜 5例 ,D级膜 1例。C级膜中 ,1例既表达了IL 1β又表达了IL 6mRNA ,1例IL 1β、IL 6、IL 8和TNF αmRNA 4者均表达 ,表达IL 1βmRNA和TNF αmRNA者 1例 ,2例有IL 6和TNF αmRNA两者表达 ,D级膜 1例单独表达IL 1βmRNA。 结论 IL 1β、IL 6、IL 8和TNF α参与了PVR增生膜的形成过程 ,这些炎性因子的产生可能与NF κB激活有关。

血小板源性生长因子α和β受体酪氨酸激酶抑制剂对兔PVR的治疗作用

目的 评价特异性的血小板源性生长因子 (PDGF) α受体酪氨酸激酶阻断剂AG12 96和 β受体酪氨酸激酶阻断剂AG12 95对兔PVR的治疗作用。 方法 兔结膜成纤维细胞结膜成纤维细胞培养 ,用MTT法检测PDGF AA和 BB以及AG12 95和AG12 96对兔结膜成纤维细胞的增殖状况的影响。建立PVR动物模型 ,玻璃体腔内分别给予AG12 95和AG12 96 ,用牵引性视网膜脱离 (tractionalretinaldetachment,TRD)的发生率评价药物的体内疗效。眼视网膜电图检查和HE染色分析药物的毒性。结果 体外 10 μmol·L-1的AG12 95和AG12 96均可显著抑制由PDGF AA和 BB诱导的成纤维细胞的增生 ,体内 10 0 μmol·L-1AG12 95和AG12 96均减缓了兔TRD的发生 ,但AG12 95的作用仅持续至 14d。相同浓度的AG12 96和AG12 95相比 ,作用更持久。在 2个治疗组中 ,均未发现明显的网膜毒性。结论 特异性的PDGF α受体酪氨酸激酶抑制剂AG12 96可显著抑制兔TRD的发生 ,其作用明显强于PDGF β受体酪氨酸激酶抑制剂AG12 95 ,提示PDGF对PVR的促进作用主要由α受体介导 。

氟尿嘧啶聚乳酸微球在PVR家兔体内的研究

考察了在增生性玻璃体视网膜病变(PVR)家兔玻璃体中植入氟尿嘧啶聚乳酸微球后的体内药物动力学和药效学。采用HPLC法测定房水中药物浓度。结果表明,制品的体内消除半衰期从0.6h延长至379h。体外累积释放率与体内相应时间的吸收分数呈明显的正相关。药效学结果根据Ryan分级法进行评价,t检验结果表明微球组与生理盐水对照组、注射液组视网膜脱离发生率有显著性差异(P<0.01),后两组间无显著性差异(P>0.05)。