Proliferative vitreoretinopathy and its relationship with inflammatory serum biomarkers

AIM:To analyze if a relationship between levels ofinflammatory serum biomarkers and severity of primaryproliferative vitreoretinopathy(PVR)exists.METHODS:A retrospective case-control study.Thehealthy adult patients with rhegmatogenous retinaldetachment and primary PVR were included in the PVRgroup.For the control group,healthy adults who underwentcataract surgery were included.The grade of PVR wasclassified according to the Retinal Society TerminologyCommittee.Blood samples were obtained before surgery,and processed in MYTHIC 18.Measures of interest wereneutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyteratio(PLR),and lymphocyte-to-monocyte ratio(LMR),thetime between the decrease in visual acuity and surgery,PVRgrade,type of surgery,final best corrected visual acuity,andrate of re-detachment.RESULTS:Totally 240 patients were included,120 ineach group,79(65.8%)and 56(46.7%)were male in thePVR and control group,respectively.PVR A had greaterlevels of monocytes(0.28±0.18 vs 0.12±0.32,P=0.002),neutrophils(4.59±1.51 vs 3.92±1.27,P=0.006),and LMR(9.32±4.42 vs 7.43±3.90,P=0.01).PVR B had a greatermonocyte count(0.30±0.13 vs 0.12±0.32,P=0.001),andPVR C demonstrated higher levels in monocytes(0.27±0.12vs 0.12±0.32,P=0.004),neutrophils(4.39±1.13 vs3.92±1.27,P=0.004),and LMR(9.63±3.24 vs 7.43±3.90,P=0.002)compared to control,respectively.An LMR cut-offvalue of 9.38 predicted PVR with a sensibility of 54.2%andspecificity of 77.5%and NLR cut-off of 1.70 predicted PVRwith a sensibility of 62%and specificity of 54.2%.CONCLUSION:Patients with primary PVR demonstrategreater neutrophil,monocyte,and LMR levels than thecontrol group.Cut-off values obtained from ratios could beuseful in a clinical setting when no posterior view of thefundus is possible due to media opacity.

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.

Immunocytochemical Study of Cells in the Vitreous of Proliferative Vitreoretretinopathy

Purpose: To identify the cellular components of vitreous samples obtained during vit-rectomy for proliferative vitreoretinopathy(PVR).Methods: With the use of three intermediate filament (IF) proteins, vimentin, glialfibrillary acidic protein (GFAP), and cytokeratin (CK), cytocentrifuge slides of 14fresh vitreous aspirates were detected with immunohistochemical technique.Results: All the specimens contained epithelial-like proliferative cells with or withoutpigment and some membrane-like pieces. Immunocytochemical staining showed that76.0-90.0% cells stained for CK, 17.4-29.6% cells expressed GFAP, and 80.1-91.0% cells were positive for vimentin.Conclusions : Majority of cells in the vitreous samples originated from retinal pigmentepithelial cells (RPE) and glial cells in PVR. Expression of IF proteins may be determinedby tissue of origin and local microenvironment. Eye Science 1999 ; 15; 13 - 16.

PI3K/AKT/mTOR signaling pathway inhibitors in proliferation of retinal pigment epithelial cells

AIM: To determine whether the PI3K/AKT/mTOR pathway is activated in proliferative vitreoretinopathy (PVR) in homo-sapiens. METHODS: The retina of controls and patients with PVR were collected and their levels of PI3K, phospho-AKT, phospho-mTOR, phospho-p70S6k and phospho-4EBP-1 were determined by Western blot. The cultured human retinal pigment epithelial cell line D407 was treated with a specific mTOR inhibitor, rapamycin (RAPA) or a PI3K inhibitor, LY294002, of various concentrations and durations. Cell morphology was observed by phase contrast microscopy and the proliferation and apoptosis of treated cells were determined by MTT assay and flow cytometry. RESULTS: Levels of PI3K, phospho-AKT, phospho-mTOR, phospho-P70S6K and phospho-4EBP1 was increased in the retina in PVR (P <0.05). In D407 cells, both RAPA and LY294002 significantly inhibited cell proliferation and cell cycle progression, and promoted apoptosis (P <0.05); morphologically, the cells became smaller. Both RAPA and LY294002 reduced levels of phospho-AKT, phospho-mTOR, phospho-p70S6k and phospho-4EBP1 expression (P <0.05). RAPA, but not LY294002, had no significant effect on PI3K expression. CONCLUSION: PI3K/AKT/mTOR signaling pathway is highly activated in the retinal pigment epithelial cells of PVR. The inhibitors of PI3K/AKT/mTOR signaling pathway, RAPA and LY294002, could inhibited the PI3K/AKT/mTOR signaling pathway by reducing the levels of phosphorylation of mTOR pathway components.

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。

Artesunate inhibits proliferation and migration of RPE cells and TGF-β2 mediated epithelial mesenchymal transition by suppressing PI3K/AKT pathway

AIM:To study the braking effectiveness of artesunate on transforming growth factor(TGF)-β2 mediated epithelial-mesenchymal transition(EMT)in retinal pigment epithelium(RPE)in vitro.METHODS:The fostered ARPE-19 cells were processed with artesunate alone or combined with the TGF-β2.The CCK-8 examination was utilized to test the cell propagation.Cell migration was detected by scratch as well as the Transwell examination.The EMT characters and activation of PI3K/Akt signal channel were estimated by Western blotting and immunofluorescence.The Western blotting was utilized in order to confirm the vitreous of controls as well as patients with proliferative vitreoretinopathy(PVR)were collected and the levels of PI3K,phospho-PI3K,Akt.RESULTS:Disposal of ARPE-19 cells with artesunate(50-150μmol/L)obviously suppressed their propagation and immigration,which dependent on the concentration and time.Artesunate suppressed the EMT which was induced by TGF-β2 in ARPE-19 cells through sustaining the expression of vimentin andα-SMA through the suppression of PI3K,phospho-PI3K,phospho-Akt and Akt.Levels of PI3K,phospho-PI3K,AKT and phospho-Akt was increased in the vitreous in PVR(P<0.05).CONCLUSION:Such findings indicate that PI3K/Akt signal channel is highly activated in vitreous of PVR.Artesuante is an operative depressor of the propagation,immigration and TGF-β2-mediated EMT of ARPE-19 cells by reduced the expression of PI3K/Akt channel.

血清和玻璃体中miR-126和miR-325与增生性玻璃体视网膜病变严重程度的关系

目的:探讨血清和玻璃体中miR-126和miR-325与增生性玻璃体视网膜病变(PVR)严重程度的关系。方法:回顾性研究。选取2019-10/2022-10在本院治疗的PVR患者100例100眼。按照视网膜病变程度分为轻度组42眼和重度组58眼。选取同期因眼外伤在本院进行玻璃体切除术无视网膜病变的患者30例30眼为对照组。采用荧光定量PCR检测血清和玻璃体中miR-126和miR-325表达水平;ELISA检测血清、玻璃体中转化生长因子-β(TGF-β)、血小板衍生生长因子(PDGF)、血管内皮生长因子(VEGF)、肿瘤坏死因子-α(TNF-α)水平;Pearson法分析血清和玻璃体中miR-126和miR-325水平与TGF-β、PDGF、VEGF、TNF-α水平的相关性;采用Logistic多因素分析影响发生重度PVR的因素。结果:PVR患者血清和玻璃体中miR-126水平较对照组降低,且重度组低于轻度组(均P<0.05);miR-325水平较对照组升高,且重度组高于轻度组(均P<0.05)。重度组患者血清和玻璃体中TGF-β、PDGF、VEGF、TNF-α水平较轻度组均上升(均P<0.05)。PVR患者血清和玻璃体中miR-126水平与miR-325、TGF-β、VEGF、TNF-α、PDGF水平均呈负相关(均P<0.05),miR-325与TGF-β、VEGF、TNF-α、PDGF水平均呈正相关(均P<0.05)。Logistic回归分析显示,血清和玻璃体中miR-325、TGF-β、PDGF、TNF-α均是发生重度PVR的危险因素,miR-126是保护因素(P<0.05)。结论:随PVR疾病的加重,患者血清和玻璃体中miR-126表达降低,miR-325表达升高,且与TGF-β、TNF-α、VEGF、PDGF具有相关性。

Effects of PDTC on the Proliferation and PCNA Expression of Human Retinal Pigment Epithelial Cells

To investigate the effects of pyrrolidine dithiocarbamate （PDTC） on the proliferation and PCNA （proliferating cell nuclear antigen） expression of cultured human retinal pigment epithelium cells, human retinal pigment epithelium cells （RPE） were cultured from normal adults who died accidentally. The effects of PDTC on the proliferation of RPE cells were examined by using methyl thiazlyl tetrazolium （MTT） assay. The effects of PDTC on the PCNA expression of RPE cells were immunohistochemically examined by employing biological image analysis system （BIAS）. After treatment with PDTC of various of concentration ranging from 0.062 to 1 g/L for 24 h, or concentrations ranging from 0.031 to 1 g/L, the proliferation of RPE cells decreased in a dose-dependent manner. After treatment with PDTC of concentration varying from 0. 062 to 1 g/L for 24 h, the PCNA expression was also suppressed in a dose-dependent manner. It is concluded that PDTC can inhibit the proliferation of RPE cells in vitro in a dose-and time-dependent manner, at least in part, by down-regulating the expression of PCNA. PDTC may be used to prevent and treat the proliferative vitreoretinopathy （PVR）.

中药单体干预增生性玻璃体视网膜病变的研究进展

增生性玻璃体视网膜病变(PVR)是导致孔源性视网膜脱离手术失败和复发的主要原因。目前临床治疗PVR多以手术为主,但存在一定不足,因此,需要寻找新的药物疗法。中药单体兼有中药与化学药的双重优势,我国传统中药与中药单体在PVR治疗尤其是视网膜保护方面具有独特优势,逐渐成为了研究热点。本文对近年来中药单体治疗PVR的文献进行综述,发现姜黄素、藏红花素、槲皮素等中药单体可通过降低血小板源性生长因子、转化生长因子、表皮生长因子等因子的表达,抑制上皮细胞—间充质转化的生物学过程,防止PVR的发生。这些中药单体的发现对后续新药的研发可提供新的选择,为PVR的治疗提供更多元化的方法。

MeCP2诱导的视网膜色素上皮细胞转录组和m6A的改变

目的探讨重组人甲基CpG结合蛋白2(MeCP2)处理的视网膜色素上皮(RPE)细胞中mRNA和N6-甲基腺嘌呤(m6A)改变及其机制。方法将传代ARPE-19细胞贴壁培养后分为正常对照组和MeCP2组,正常对照组细胞采用正常培养液培养,MeCP2组细胞于含终质量浓度20 ng/ml重组人MeCP2蛋白培养液中,连续培养72 h。提取细胞内总RNA进行转录组测序(RNA-seq)和甲基化免疫共沉淀测序(MeRIP-seq)分析。采用edgeR软件包根据P<0.05筛选差异表达基因(DEGs)和差异甲基化基因(DMGs)。采用基因本体论(GO)富集分析对差异基因进行生物学功能描述,采用京都基因和基因组百科全书(KEGG)进行通路富集分析。筛选出DEGs与DMGs交集的基因,采用实时荧光定量PCR技术检测各组差异基因mRNA表达水平。结果共筛选出DEGs 100个,DMGs 7441个,富集分析发现DEGs与细胞外基质(ECM)-受体相互作用、细胞分裂、细胞周期和磷脂酰肌醇3激酶/蛋白激酶B(PI3K/AKT)信号通路等相关,DMGs与微管细胞骨架、血管生成、表皮生长因子受体(ErbB)信号通路、晚期糖基化终末产物(AGEs)-糖基化终末产物受体(RAGE)信号通路、哺乳动物雷帕霉素靶蛋白(mTOR)信号通路、Notch信号通路和转化生长因子β(TGF-β)信号通路等相关。DEGs中24个基因表达增加,76个基因表达减少;DMGs中5个基因含有高甲基化峰,7439个基因含有低甲基化峰,注释峰后,正常对照组有7626个基因发生m6A甲基化,MeCP2组有8006个基因发生m6A甲基化,2个组间有7360个交集基因。正常对照组和MeCP2组的m6A甲基化富集于转录本的CDS、内含子和3'-非翻译区(3'UTR)区域,其甲基化比例分别为23.62%/22.27%、48.53%/48.35%和23.66%/25.28%。联合分析发现2个上皮-间充质转化(EMT)相关基因CSPG 5和RBP1的mRNA和m6A水平均降低。荧光定量PCR结果显示,MeCP2组GSPG5、RBP1、ZNF484 mRNA相对表达量均明显低于正常对照组,差异均有统计学意义(t=7.885、7.613、7.345,均P<0.01)。结论RPE细胞中MeCP2对EMT的调控机制与m6A甲基化修饰相关。CSPG 5和RBP 1基因可能是m6A甲基化的靶基因,参与MeCP2调控的EMT过程。

中医药治疗增生性玻璃体视网膜病变研究进展

增生性玻璃体视网膜病变(PVR)是导致孔源性视网膜脱离手术失败和复发的主要原因,目前西医治疗以手术为主,但存在不足之处,中医药治疗PVR成为目前的研究热点。本文旨在综述近年来中、西医对PVR的认识,并整理归纳已被证实具有防治效果的中药单体及复方制剂的相关文献,发现PVR与肝、脾、肾等脏腑功能状态密切相关,为中医药在PVR治疗的应用提供了理论基础。同时,藏红花酸、三七总皂苷、青蒿琥酯等中药单体以及活血散结方、散血明目片、大黄蛰虫丸等中药复方制剂能通过多条信号通路,抑制视网膜色素上皮细胞增殖迁移和上皮-间质转化等生物学进程,进而起到防治PVR的作用。这些研究为中医药防治PVR提供科学依据,提示中医药治疗PVR具有潜力和优势。

Chronic hypotony management using endoscopy-assisted vitrectomy after severe ocular trauma or vitrectomy

·AIM: To report outcomes of endoscopy-assisted vitrectomy(EAV) in patients with chronic hypotony following severe ocular trauma or vitrectomy.·METHODS: This was a retrospective, noncomparative case series. Ciliary bodies were evaluated using ultrasound biomicroscopy pre-operatively and direct visualisation intraoperatively. All selected individuals(seven patients/seven eyes) underwent EAV. Removal of ciliary membrane and traction, gas/silicone oil tamponade(GT/SOT), and scleral buckling(SB) were performed in selected eyes. Outcome measurements mainly included intraocular pressure(IOP) and best-corrected visual acuity(BCVA).·RESULTS: Seven eyes from 7 male aphakic patients with a mean age of 45(range, 20-68)y were included in this study;the average follow-up time was 12(9-15)mo. GT was performed in 2 eyes;membrane peeling(MP) and SOT in 2 eyes;and MP, SOT, and SB in 3 eyes. The mean preand post-operative IOP were 4.5(range, 4.0±0.11 to 4.8±0.2) mm Hg and 9.9(range, 5.6±0.17 to 12.1±0.2) mm Hg at 52wk(12mo), respectively. BCVA improved in six eyes;one eye still showed light perception, and no bulbi phthisis was observed.·CONCLUSION: Endoscopy offers improved judgment and recognition and has an improved prognosis for chronic hypotony. Therefore, endoscopy can be an effective and promising operative technique for chronic traumatic hypotony management.