Progressive endothelial cell injury of retinal vascular is a vital factor in diabetic retinopathy (DR) pathogenesis. Mesenchymal stem cells-derived small extracellular vesicles (MSC-sEVs) showed beneficial effects on DR. However, the effects of MSC-sEVs on endothelial dysfunction of DR and the mechanism is still unclear. In this study, MSC-sEVs mitigated retinal blood-retina barrier (BRB) impairment in rats with streptozotocin (STZ)-induced DR by reducing ferroptosis in vivo and in vitro. MSC-sEVs miRNA sequencing analysis revealed that miR-125b-5p may mediate human retina microvascular endothelial cells (HRMECs) ferroptosis and P53 as a downstream target based on dual-luciferase reporter assays. Silencing miR-125b-5p in MSC-sEVs reversed the therapeutic effects of MSC-sEVs on rats with DR and advanced glycation end products (AGEs)-treated HRMECs. Additionally, overexpression of miR-125b-5p could diminish ferroptosis in HRMECs, and this effect could be effectively reversed by overexpressing P53. This study indicated the potential therapeutic effect of MSC-sEVs on vascular endothelial function maintenance and that the delivery of sEVs carrying miR-125b-5p could prevent endothelial cell ferroptosis by inhibiting P53, thereby protecting the BRB.

Abstract Progressive endothelial cell injury of retinal vascular is a vital factor in diabetic retinopathy (DR) pathogenesis. Mesenchymal stromal cells-derived small extracellular vesicles (MSC-sEVs) showed beneficial effects on DR. However, the effects of MSC-sEVs in endothelial dysfunction of DR and the mechanism is still unclear. In this study, MSC-sEVs mitigated retinal blood-retina barrier(BRB) impairment in rats with streptozotocin (STZ)-induced DR by reducing ferroptosis in vivo and in vitro. MSC-sEVs miRNA sequencing analysis revealed that miR-125b-5p may mediate HRMEC ferroptosis and P53 as a downstream target based on dual-luciferase reporter assays. Silencing miR-125b-5p in MSC-sEVs reversed the therapeutic effects of MSC-sEVs on rats with DR and advanced glycation end products (AGE)-treated HRMECs. Additionally, overexpression of miR-125b-5p could diminish ferroptosis in HRMECs, and this effect could be effectively reversed by overexpressing P53. This study indicated the potential therapeutic effect of MSC-sEVs on vascular endothelial function maintenance and that the delivery of sEVs carrying miR-125b-5p could prevent endothelial cell ferroptosis by inhibiting P53, thereby protecting the BRB.

·AIM:To analyze the correlation between ocular surface status and serum lipids in patients with meibomian gland dysfunction(MGD)during pregnancy,and to provide new ideas for the management and treatment of MGD during pregnancy. ·METHODS:Totally 120 pregnant women(240 eyes)treated in our hospital from May 2021 to May 2022 were selected and they were divided into MGD group(60 cases,120 eyes)and control group(60 cases,120 eyes)according to the presence or absence of MGD.All subjects received the ocular surface disease index scores(OSDI)and underwent examinations of meibomian gland morphology and function,tear film and blood lipid. ·RESULTS:The scores of OSDI,the related indexes of meibomian gland,corneal fluorescein staining(FL)scores,total cholesterol(TC),triglyceride(TG)and low density lipoprotein-cholesterol(LDL-C)in the MGD group were significantly higher than those in the control group(P＜0.05).The scores of fluorescein breakup time(FBUT),Schirmer I test(SIt)and high-density lipoprotein cholesterol(HDL-C)in the MGD group were significantly lower than those in the control group(P＜0.05).Correlation analysis showed that the scores of TG,TC,LDL-C were negatively correlated with the values of FBUT(rs=-0.702,-0.647,-0.710,all P＜0.001). ·CONCLUSION:The level of blood lipids in pregnant patients with MGD is significantly increased,and the levels of TC,TG and LDL-C may be related to the stability of tear film.

Herpes simplex virus type 1 (HSV-1) infection of the eyes results in herpes simplex keratitis (HSK), which has led to vision loss and even blindness in patients. However, the rate of drug resistance in HSV is on the rise; therefore, new antiviral agents with sufficient safety profiles must be developed. At present, we assessed the anti-HSV-1 activity of 502 natural compounds and their ability to reduce the HSV-1-induced cytopathic effect. We chose harmol for further studies because it exhibited the highest antiviral activity. We found that harmol inhibited both HSV-1 F and HSV-1/153 (a clinical drug-resistant strain) replication, with an EC50 of 9.34 µM and 5.84 µM, respectively. Moreover, harmol reduced HSV-1 replication in corneal tissues and viral progeny production in tears, and also alleviated early corneal surface lesions related to HSK. For example, harmol treatment preserved corneal thickness and nerve density in HSK mice. Interestingly, harmol also showed a promising antiviral effect on HSV-1/153 induced HSK in mouse model. Furthermore, harmol combined with acyclovir (ACV) treatment showed a greater antiviral effect than either one alone in vitro. Therefore, harmol may be a promising therapeutic agent for managing HSK.

Diabetic retinopathy (DR) is recognized as the most prevalent retinal degenerative disorder. Inflammatory response usually precedes microvascular alteration and is the primary factor of diabetic retinopathy. Activated microglia express many pro-inflammatory cytokines that exacerbate retina inflammation and disruption. In the present study, we found that MSCs alleviated blood-retina barrier (BRB) breakdown in diabetic rats, as evidenced by reduced retinal edema, decreased vascular leakage, and increased occludin expression. The MSC-treated retinal microglia exhibited reduced expression of M1-phenotype markers in the diabetic rats, including inducible nitric oxide synthase (iNOS), CD16, and pro-inflammatory cytokines. On the other hand, MSCs increased the expression of M2-phenotype markers, such as arginase-1 (Arg-1), CD206, and anti-inflammatory cytokines. HMGB1/TLR4 signaling pathway is activated in DR and inhibited after MSC treatment. Consistent with in vivo evidence, MSCs drove BV2 microglia toward M2 phenotype in vitro. Overexpression of HMGB1 in microglia reversed the effects of MSC treatment, suggesting HMGB1/TLR4 pathway is necessary for MSCs' regulatory effects on microglia polarization. Collectively, MSCs exert beneficial effects on DR by polarizing microglia from M1 toward M2 phenotype via inhibiting the HMGB1/TLR4 signaling pathway.

Herpes simplex virus type 1 (HSV-1) is a common virus infecting the ocular tissue. It infects eye tissues, such as the eyelid, cornea, and conjunctiva. Corneal HSV-1 infection causes herpes simplex keratitis (HSK), which can induce vision loss. Current treatments for eye infections targeting HSV-1 can led to various sequelae. Antiviral drugs only work during active viral replication, and viral resistance has been recorded in numerous cases. Therefore, it is necessary to determine the molecular mechanisms underlying HSV-1 infection and identify new antiviral drugs. There are no reports on whether PI3K can regulate SGK1 to modulate HSV-1 infection in corneal epithelial cells (CECs), or how this mechanism works. This study found that HSV-1 levels and apoptosis increased in human corneal epithelial cells (HCECs) and BALB/c mice after HSV-1 infection. Serum and glucocorticoid-regulated protein kinase 1 (SGK1) were upregulated in HCECs and corneal tissues of BALB/c mice infected with HSV-1, as evidenced by whole-transcriptome sequencing, quantitative real-time polymerase chain reaction (RT-qPCR), and immunofluorescence staining experiments. An inhibitor of SGK1 (GSK 650394) reduced SGK1 expression, HSV-1 replication, and apoptosis in CECs, as evidenced by western blotting, flow cytometry, and in cell western blotting. The phosphatidylinositol 3'-kinase (PI3K) pathway was activated in CECs infected with HSV-1. After treatment with the PI3K inhibitor (LY294002), the expression of SGK1 and Wnt signaling pathway protein β-catenin were downregulated, and the replication of HSV-1 decreased in CECs; additionally, CECs apoptosis was reduced. HSV-1 replication causes CECs apoptosis. In HSV-1 infected CECs, SGK1 expression was upregulated by activated PI3K/SGK1 signaling pathway. Additionally, SGK1 activated Wnt/β-catenin signaling pathway to promote HSV-1 replication and cause CEC apoptosis. In conclusion, SGK1 is an important target for HSK treatment.

目的:探索甲基转移酶3(METTL3)介导的N6-甲基腺苷(m6 A)甲基化修饰在脉络膜新生血管发病中对血管内皮细胞生物学活性的调控作用及机制.方法:将体外培养的人脐静脉内皮细胞(HUVEC)分为:对照组(正常培养)、低密度脂蛋白(LDL)组、荧光标记LDL(Dil-LDL)组、12.5μg/mL、25μg/mL氧化低密度脂蛋白(ox-LDL)组、12.5μg/mL、25μg/mL荧光标记ox-LDL(Dil-ox-LDL)组、DMSO组、STM2457(METTL3抑制剂)组、DAPT组;将体外培养的猴视网膜-脉络膜内皮细胞(RF/6A)分为:对照组、DMSO组、12.5μg/mL ox-LDL组、DAPT组.荧光显微镜观察细胞内吞脂蛋白水平,dot blot检测m6A甲基化水平,Western blot检测METTL3及血管形成相关蛋白的表达水平,实时荧光定量聚合酶链反应(RT-qPCR)检测METTL3及血管形成相关标志物的mRNA表达水平,免疫荧光检测METTL3表达水平及定位,transwell实验检测细胞迁移能力,体外成管实验检测细胞血管形成能力.结果:与对照组相比,Dil-LDL组、12.5μg/mL、25μg/mL Dil-ox-LDL组细胞内荧光标记的脂蛋白含量显著升高,12.5μg/mL、25μg/mL ox-LDL组m6 A甲基化水平显著升高(均P<0.05),METTL3蛋白表达水平显著升高(均P<0.01),细胞迁移及血管形成能力显著上升(均P<0.01),12.5μg/mL ox-LDL组METTL3 mRNA表达水平显著上调(P<0.05);与DMSO组相比,STM2457组m6 A甲基化水平显著降低(P<0.05),METTL3的蛋白及mRNA表达水平无显著差异(均P>0.05),血管内皮生长因子(VEGF)等血管形成相关标志物表达水平显著下降(均P<0.05),细胞迁移及血管形成能力显著下降(均P<0.01),NICD表达水平显著下降(P<0.05);与DMSO组相比,DAPT组NICD、VEGF表达水平显著下降(均P<0.05),HUVEC及RF/6A细胞迁移及血管形成能力显著下降(均P<0.01).结论:METTL3介导的m6 A甲基化修饰在脉络膜新生血管发病中可经Notch通路促进血管内皮细胞的血管形成.

BACKGROUND:Corneal neovascularization (CNV) is a symptom of herpes simplex keratitis (HSK), which can result in blindness. The corneal angiogenesis brought on by herpes simplex virus type 1 (HSV-1) is strongly affected by vascular endothelial growth factor A (VEGFA). The N6-methyladenosine (m6A) modification catalyzed by methyltransferase-like 3 (METTL3) is a crucial epigenetic regulatory process for angiogenic properties. However, the roles of METTL3 and m6A in HSK-induced CNV remain unknown. Here, we investigated these roles in vitro and in vivo.METHODS:A PCR array in HSV-1-infected human umbilical vein endothelial cells (HUVECs) was used to screen for METTL3 among the epitranscriptomic genes. Tube formation and scratch assays were conducted to investigate cell migration capacity. The global mRNA m6A abundance was evaluated using a dot blot assay. Gene expression was assessed by RT-qPCR, western blotting, and fluorescence immunostaining. In addition, bioinformatic analysis was conducted to identify the downstream molecules of METTL3 in HUVECs. METTL3 knockdown and STM2457 treatment clarified the specific underlying molecular mechanisms affecting HSV-1-induced angiogenesis in vitro. An acute HSK mouse model was established to examine the effects of METTL3 knockdown or inhibition using STM2457 on pathological angiogenic development in vivo.RESULTS:METTL3 was highly upregulated in HSV-1-infected HUVECs and led to increased m6A levels. METTL3 knockdown or inhibition by STM2457 further reduced m6A levels and VEGFA expression and impaired migration and tube formation capacity in HUVECs after HSV-1 infection. Mechanistically, METTL3 regulated LRP6 expression through post-transcriptional mRNA modification in an m6A-dependent manner, increasing its stability, upregulating VEGFA expression, and promoting angiogenesis in HSV-1-infected HUVECs. Furthermore, METTL3 knockdown or inhibition by STM2457 reduced CNV in vivo.CONCLUSION:Our findings revealed that METTL3 promotes pathological angiogenesis through canonical Wnt and VEGF signaling in vitro and in vivo, providing potential pharmacological targets for preventing the progression of CNV in HSK.

目的:探讨N6-甲基腺嘌呤(N6-methyladenosine,m6A)甲基化转移酶3(METTL3)在糖尿病性白内障发病中的作用机制.方法:用低糖和高糖培养基培养人晶状体上皮细胞系(SRA01/04)24h 后,采用 RT-qPCR 和 Western blot 实验检测细胞的上皮-间质转分化(EMT)指标:E-钙黏蛋白(E-Cadherin)、N-钙黏蛋白(N-Cadherin)、紧密连接蛋白1(ZO-1)和α-平滑肌肌动蛋白(α-SMA)的变化情况;transwell和划痕实验检测细胞迁移能力.采用免疫荧光染色检测人晶状体前囊膜组织中METTL3的表达量及定位,m6A dot blot实验检测在低糖和高糖培养基中培养24h细胞的m6A甲基化水平,RT-qPCR和Western blot实验检测细胞中METTL3的RNA和蛋白表达量.加入METTL3抑制剂的培养基中培养24h的细胞,RT-qPCR和Western blot实验检测EMT指标的变化情况;m6A dot blot实验检测细胞m6A甲基化水平;Transwell和划痕实验检测细胞迁移能力.免疫荧光染色检测细胞中转化生成因子β(TGFβ1)的表达;RT-qPCR和Western blot实验检测细胞中的TGFβ1和SNAIL的表达量.结果:与低糖条件相比,高糖条件能够促进细胞EMT的发生,促进METTL3的表达和上调了细胞总RNA的m6A甲基化水平(P＜0.05).高糖能够促进细胞的迁移能力.糖尿病性白内障患者晶状体前囊膜中METTL3表达较单纯年龄相关性白内障患者增高.与高糖+DMSO组相比,加入METTL3抑制剂STM2457,能够抑制细胞的EMT发生,抑制TGFβ1和SNAIL的表达,抑制细胞总RNA的m6A甲基化水平(均P＜0.05).加入METTL3抑制剂STM2457后细胞迁移能力较高糖+DMSO组降低.结论:m6A甲基化转移酶METTL3通过激活TGFβ1/SNAIL通路促进了在高糖条件下人晶状体上皮细胞的EMT发生从而诱导糖尿病性白内障的发生.

目的 分析妊娠期干眼综合征患者泪液状态与视觉质量的相关性.方法 比较妊娠期干眼综合征患者50例(干眼组)和正常妊娠期妇女50例(对照组)的泪液状态和视觉质量指标,采用Pearson相关分析视觉质量与其他指标的相关性.结果 与对照组相比,干眼组眼表疾病指数评分、客观散射指数(OSI)、角膜荧光素染色评分升高(P＜0.01),泪膜破裂时间(BUT)、调制传递函数(MTF)截止频率、斯特列尔比值(SR)、OV100％、OV20％、OV9％降低(P＜0.01).干眼组MTF截止频率、SR、O V100％、OV20％、OV9％与 BUT 呈正相关(r=0.712、0.624、0.627、0.610、0.712,P＜0.01),OSI与BUT呈负相关(r=-0.735,P＜0.01).结论 妊娠期干眼综合征患者的视觉质量低于正常妊娠期妇女,可能与妊娠期泪膜稳定性下降有关.

AIM: To analyze ocular wavefront aberrations and scattering parameters changes in patients with meibornian gland dysfunction(MGD)and aqueous deficient dry eye(ADDE), and assess the visual quality of patients with two types of dry eye syndromes.METHODS:There were 25 patients with MGD, 25 patients with ADDE and 25 healthy controls treated in our hospital from January to October 2018 were included in this study. Ocular surface disease index questionnaire(OSDI)and tear film correlation examination were performed in three groups. The tear film correlation examination included tear break-up time(TBUT), Schirmer test( SⅠt )and cornea fluorescein staining(FL). The root mean square of total high order aberration(HO), comatic aberration(CA), trefoil aberration(TA)and spherical aberration(SA)were recorded with i-Trace visual function analyzer. The scattering values were recorded by the double-pass Optical Quality Analysis System(OQAS Ⅱ), including the modulation transfer function(MTF cutoff ), Strehl ratio(SR)and objective scattering index( OSI ). Three groups of subjects kept their eyes open for 20s, the mean value of OSI was recorded using OQAS Ⅱ tear film analysis program.RESULTS:The OSDI score in MGD group was significantly higher than that in ADDE group(38.2±5.6 vs 32.2±7.2, P<0.01). The SⅠT score in ADDE group was significantly lower than that in MGD group(1.98±0.92 vs 12.52±6.80mm/5min, P<0.001). The TBUT and FL staining score were lower in MGD group than those in ADDE group(TBUT: 3.27±1.91 vs 6.02±1.05s, FL:3.27±2.18 vs 6.23±2.19, all P<0.001). There was no significant difference in HO, CA, TA and SA between MGD Group and ADDE group(HO: 0.385±0.081 vs 0.344±0.092, CA:0.210±0.062 vs 0.175±0.075, TA:0.107±0.056 vs 0.086±0.042, SA:0.322±0.078 vs 0.273±0.097, HO:t=1.67, P>0.05; CA: t=1.80, P>0.05; TA: t=1.50, P>0.05; SA: t=1.97, P>0.05). There was no statistically significant differences between MGD group and ADDE group with the value of MTF cutoff, SR and OSI(MTF cutoff: 33.28±8.28 vs 37.12±9.53, SR: 0.19±0.06 vs 0.22±0.08, OSI:1.30±0.32 vs 1.12±0.52, MTF cutoff: t=1.52, P>0.05; SR: t=1.50, P>0.05; OSI: t=1.47, P >0.05). In the condition of not blinking, the mean value of OSI in MGD group was significantly higher than that in ADDE group(2.386±0.118 vs 1.554±0.058, P<0.001).CONCLUSION:In the treatment of symptoms of patients with dry eye, improving the visual quality of patients should also be considered. The visual quality in patients with MGD is more serious than those with ADDE. The OSI related parameters seem to be sensitive indicators indexes to evaluate the dynamic changes of tear film-related visual quality in dry eye patients.

Objective To investigate the clinical characteristics and treatment prognosis of laser-induced macular injury. Methods 6 patients（ 6 eyes） with macular injury caused by laser irradiation were retrospectively analyzed. Among them,5 cases（ 5 eyes） were male and 1 case（ 1 eye） was female. The age was 21. 3 ± 4. 8 years old,including 1 case and 1 eye（ 16. 7%） under 18 years old. The best corrected visual acuity,fundus condition and macular optical coherence tomography（ OCT） were recorded at the time of admission. Anti inflammatory,hemostatic and detumescence treatments were given according to the patient’s condition,and surgery was performed if necessary. Best corrected visual acuity and macular OCT were followed up after discharge. Results 6 eyes of 6 cases were all right eyes. The best corrected visual acuity（ BCVA） ≥ index and ＜ 0. 12 cases after injury; 3 cases were ≥ 0. 1 and ＜ 0. 2,1 cases were ≥ 0. 2 and ＜0. 3. Macular hole was formed in 6 cases and vitrectomy was performed in 5 cases. After treatment,the best corrected visual acuity improved in 5 cases,decreased in 1 case,≥ 0. 1 and ＜ 0. 3 5 cases; 1 case was ≥ 0. 3 and ＜ 0. 5. The inner segment/outer segment（ IS/OS） layer was damaged in all cases,including 3 cases of rupture and 3 cases of continuous incomplete. Conclusions in the early stage of laser-induced macular injury,macular edema and hemorrhage may appear.With the gradual absorption of edema,lamellar holes may be formed in some patients,followed by full-thickness holes,and some may form submacular scars. In this study,the improvement of visual acuity may be related to the gradual regression of macular edema. However,due to the permanent rupture of IS/OS,the improvement of visual acuity in some cases is not obvious even if there is a small increase.

Herpes Simplex Virus 1 (HSV-1) invades corneal nerves upon its infection of the cornea and then establishes latency in the trigeminal ganglion (TG). The latent virus in TG is often reactivated and travels back to the cornea, causing recurrent herpes simplex keratitis (HSK). The entry of HSV-1 into the corneal nerve is considered the initial step of infection resulting in HSV-1 latency and HSK recurrence. Several gD and gB receptors have been identified, including nectin-1, herpes virus entry medium (HVEM) and 3-O-sulfated heparan sulfate (3-OS-HS) as gD receptors, and non-muscle myosin heavy chain IIA (NMHC-IIA), NMHC-IIB and myelin-associated glycoprotein (MAG) as gB receptors. However, which receptors contribute to the entry of HSV-1 into corneal nerves are yet to be determined. This study observed that receptors nectin-1, HVEM, 3-OS-HS, NMHC-IIA, and NMHC-IIB, not MAG, were expressed in healthy corneal nerves. Further, we cultured TG neurons extracted from mice in vitro to screen for functional gD/gB receptors. Both in vitro siRNA knockdown and in vivo antibody blocking of either nectin-1 or NMHC-IIB reduced the entry and the replication of HSV-1 as shown by qPCR analysis and immunofluorescence measure, respectively. Also, we observed that the re-localization and the upregulation expression of NMHC-IIB after HSV-1 exposure were inhibited when gD receptor nectin-1 was knocked down. These data suggest that nectin-1 was the main gD receptor and NMHC-IIB was the main gB receptor in mediating HSV-1 entry and hold promise as therapeutic targets for resolving HSV-1 latency and HSK recurrence.

Background The early visual qualities of patients with moderate myopia were evaluated after small incision lenticule extraction (SMILE) using different optical zones. Methods In this retrospective case study, 27 cases (51 eyes) were selected, including 10 cases in Group A (19 eyes), 6.6–6.8 mm in the optical zone, 10 cases in Group B (19 eyes), 6.4–6.5 mm in the optical zone, and 7 cases in Group C (13 eyes),6.1–6.3 mm in the optical zone. The following items were examined preoperatively and 1 month postoperatively: uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), spherical, cylinder, central corneal thickness (CCT), corneal mean curvature (CMC), total ocular aberrations (TA), total low order aberrations (tLOAs), defocus, astigmatism and total high order aberrations (tHOAs), spherical, coma, trefoil, modulation transfer function (MTF), MTF cutoff , SR, objective scatter index (OSI), point scatter function at 50 and 10% (PSF50%, PSF10%), and contrast visual acuity of 100, 20, and 9% (VA100%, VA20%, and VA9%). We compared the three groups by Kruskal-Wallis test. Wilcoxon signed ranks test was used for each group before and 1 month after surgeries. P < 0.05 was considered statistically significant. Results There was no significant difference in UCVA, BCVA, CCT, cylinder, and CMC in three groups preoperatively and 1 month postoperatively ( P > 0.05). Comparison of the aberrations of the three groups showed statistically significant difference only in TA, tLOA, defocus, astigmatism and SA preoperatively, and trefoil 1 month postoperatively( P < 0.05). The postoperative TA, tLOAs, defocus, astigmatism and trefoil of the three groups were lower than those before surgeries ( P < 0.05). The postoperative tHOAs of Group B and C was lower than those before surgeries ( P < 0.05). The MTF results showed that before surgeries, there were significant differences in three groups ( P < 0.05) in spatial frequencies 5~15 cycles per degree (cpd), and no differences in 20~30 cpd( P > 0.05), while no difference were observed in all spatial frequencies postoperatively ( P > 0.05). Comparing the preoperative and postoperative MTF values for each group, the results showed that there was a significant difference in Group C at 5~20 cpd after surgeries( P < 0.05). There was no significant difference in MTF cutoff , SR, OSI, PSF50%, PSF10%, VA100%, VA20%, and VA9% in the three groups preoperatively ( P > 0.05). One month after surgeries, higher VA9% values were measured for Group C compared to Group A and B ( P < 0.05). There was no significant difference in each group before and after surgeries ( P > 0.05). Conclusion SMILE could improve the visual qualities of patients with moderate myopia. Reducing the surgical optical zone will only affect night vision slightly.

患者男性,64岁.因左眼被拴猪绳索打伤后10 h入院,患者诉左眼在伤后3 h,即出现左眼疼痛,明显的视力下降.入院后眼部检查(图1):左眼视力光感,结膜混合性充血,角膜上皮广泛糜烂,角膜中央溃疡约2 mm,深达后弹力层,溃疡颞侧可见一纵行划痕(长约 4 mm),深达深基质层,角膜后可见色素性KP沉着,前房积脓,约3 mm,瞳孔圆,光应迟钝,瞳孔缘可见絮状纤维素样渗出,晶状体前表面中央可见色素样沉着,余结构窥不清.左眼前节相干光层析成像术(opti-cal coherence tomography,OCT )示(图 2):左眼角膜增厚(厚度为1053 um),中央区角膜基质混浊,角膜内皮皱折增厚.B型超声示:左眼前段玻璃体混浊.入院后连续3d行结膜囊分泌物细菌培养,结果均为阴性.入院后抽取0. 1 ml前房水行病原微生物宏基因检测(IngeniGen XunMinKang Biotech-nology Inc.),回报结果为大肠埃希菌感染(图3 ).诊断:(1 )左眼角膜溃疡;(2)左眼感染性眼内炎.入院后立即取结膜囊分泌物做细菌培养,给与局部地塞米松2. 5 mg+庆大霉素80 mg球结膜下注射(共5 d);局部给与左氧氟沙星眼液点左眼0. 5 h 1 次、妥布霉素滴眼液点左眼0. 5 h 1 次;阿托品眼用凝胶2次/d;全身静脉给与头孢他定注射液2. 4 g/d+莫西沙星注射液0. 4g/d+地塞米松10 mg.连续治疗3d后前房积脓消失,前房渗出明显减少;治疗第5 天前房反应消失,角膜溃疡逐渐愈合,角膜逐渐透明;治疗后10 d停用全身药物,查左眼(图4)视力:0. 4,球结膜充血较前明显减轻,角膜溃疡缩小至1 . 5 mm大小,溃疡表面光滑,颞侧划痕基本愈合,余角膜完全透明,角膜后色素性KP消失,晶状体前表面色素沉着消失,瞳孔药物性散大,玻璃体透明,患者自觉眼部疼痛症状明显减轻.眼科B型超声显示:左眼前段玻璃体混浊消失.前节OCT示(图5 ):左眼角膜中央厚度652 μm,中央区基质瘢痕愈合,内皮皱折消失.

目的 观察高度近视患者Verisyse虹膜固定型人工晶状体(IOL)植入术后10年角膜内皮细胞计数(ECD)的变化,分析其丢失影响因素,并应用眼前节相干光层析成像术(AS-0CT)评估IOL在眼内的相对位置.方法 回顾性分析2008年9月至2010年7月在我院行Verisyse IOL植入术的高度近视患者的临床资料.所有患者均于术前、术后10年进行眼科检查,术后10年应用AS-0CT测量IOL到周围组织的距离,多元线性回归分析术后10年角膜内皮细胞丢失率的影响因素.结果 IOL前表面中央和边缘到角膜内皮的最短距离分别为(2.13±0.23)mm和(1.30±0.21)mm,IOL后表面到自然晶状体前表面的距离为(0.70±0.13)mm.Verisyse植入术后10年ECD丢失率为(11.56±12.01)％,多元线性回归提示IOL前表面中央和边缘到角膜内皮的最短距离为主要影响因素.结论 Verisyse IOL植入术后10年内皮丢失与IOL前表面中央和边缘到角膜内皮的最短距离有关,建议长期随访中,要关注角膜内皮细胞丢失率及人工晶状体在前房的位置以评估其安全性.

Herpes simplex virus type 1 (HSV-1) infection induces various clinical disorders, such as herpes simplex encephalitis (HSE), herpes simplex keratitis (HSK), and genital herpes. In clinical intervention, acyclovir (ACV) is the major therapeutic drug used to suppress HSV-1; however, ACV-resistant strains have gradually increased. In the present study, harringtonine (HT) significantly inhibited infection of HSV-1 as well as two ACV-resistant strains, including HSV-1 blue and HSV-1 153. Time-of-drug addition assay further revealed that HT mainly reduced the early stage of HSV-1 infection. We also demonstrated that HT mainly affected herpes virus entry mediator (HVEM) expression as shown by qPCR, Western Blot, and Immunofluorescence. Collectively, HT showed antiviral activity against HSV-1 and ACV-resistant strains by targeting HVEM and could be a promising therapeutic candidate for mitigating HSV-1-induced-pathogenesis.

目的 采用双通道视觉质量分析系统(optical quality analysis system,OQAS)比较飞秒激光小切口基质透镜取出术(small incision lenticule extraction,SMILE)和去瓣机械法准分子激光角膜上皮瓣下磨镶术(epipolis laser in situ keratomileusis,Epi-LASIK)术后1 a患者视觉质量及眼内散射情况.方法 本研究为回顾性病例对照研究.选取2013年3月至2014年8月在中国人民解放军东部战区总医院接受角膜屈光手术的近视眼患者95例(189眼).按手术方式分为SMILE组52例(103眼),去瓣Epi-LASIK组43例(86眼).观察并比较两组患者术后1 a的裸眼视力(UCVA)、最佳矫正视力(BCVA)、眼内客观散射指数(OSI)、MTF截止空间频率(MTF cutoff)、斯特列尔比值(SR)、100%、20%、9%对比度的OQAS值(OV100%、OV20%、OV9%)和患者满意度等.结果 术后1 a,SMILE组和去瓣Epi-LASIK组UCVA较术前均显著提高(均为P<0.05);但两组间UCVA差异无统计学意义(P>0.05).术后1 a,两组BCVA与术前相比以及两组间相比差异不大,均无统计学意义(均为P>0.05).术后1 a,SMILE组和去瓣Epi-LASIK组的有效系数分别为1.039和1.038,安全性指数分别为1.066和1.046.术后1 a,两组患者OSI的差异无统计学意义(P>0.05).SMILE组MTF cutoff和SR略高于去瓣Epi-LASIK组,但差异均无统计学意义(均为P>0.05).另外,两组患者OV100%、OV20%、OV9%值随图像对比度的降低均有依次递减的趋势,但两组间差异均无统计学意义(均为P>0.05).术后1 a,SMILE组中,OSI与年龄呈正相关,与术前等效球镜度、SR呈负相关;MTF cutoff与年龄呈负相关,与SR呈正相关,而与术前等效球镜度无相关性.去瓣Epi-LASIK组中,OSI与年龄呈正相关,与术前等效球镜度、SR呈负相关;MTF cutoff与年龄成负相关,与术前等效球镜度、SR呈正相关.术后1 a,SMILE组和去瓣Epi-LASIK组的手术满意度问卷调查评分分别为(9.52±0.80)分和(9.26±0.99)分(总分为10分),差异无统计学意义(P>0.05).SMILE组眩光[(1.090±0.930)分]和干涩感[(1.126±1.152)分]的评分低于去瓣Epi-LASIK组[分别为(1.490±1.200)分和(1.861±1.496)分],差异均有统计学意义(均为P<0.05).结论 SMILE与去瓣Epi-LASIK矫正近视安全有效,术后患者都可获得良好的视力及视觉质量.其中患者对SMILE术后眩光和干涩感控制效果的满意度更高.

AIM To explore the roles of microRNA-let7c (miR-let7c) and transforming growth factor-β2 (TGF-β2) and cellular signaling during epithelial-to-mesenchymal transition (EMT) of retinal pigment epithelial cells. METHODS Retinal pigment epithelial (ARPE-19) cells were cultured with no serum for 12h, and then with recombinant human TGF-β2 for different lengths of time. ARPE-19 cells were transfected with 1×106 TU/mL miR-let7c mimcs (miR-let7cM), miR-let7c mimcs negative control (miR-let7cMNC) and miR-let7c inhibitor (miR-let7cI) using the transfection reagent. The expression of keratin-18, vimentin, N-cadherin, IKB alpha, p65 were detected by Western blot, quantitative polymerase chain reaction and immunofluorescence. RESULTS The expression of miR-let7c was dramatically reduced and the nuclear factor-kappa B (NF-κB) signaling pathway was activated after induction by TGF-β2 (P<0.05). In turn, overexpressed miR-let7c significantly inhibited TGF-β2-induced EMT (P<0.05). However, miR-let7c was unable to inhibit TGF-β2-induced EMT when the NF-κB signaling pathway was inhibited by BAY11-7082 (P<0.01). CONCLUSION The miR-let7c regulates TGF-β2-induced EMT through the NF-κB signaling pathway in ARPE-19 cells.

患者女性,51岁.因"双眼畏光异物感、视力进行性下降25年"入院.患者最早于1993年首次出现双眼畏光、异物感,当地医院对症治疗后好转.此后双眼眼红、眼部刺激症状反复出现,并伴有全身乏力、浮肿等表现.2000年因双眼视力下降于河南省眼科研究所就诊,诊断为"双眼边缘性角膜变性",予对症治疗后患者自述改善不明显.2004年6月再次出现浮肿,查抗髓过氧化物酶抗体(MPO-ANCA)阳性,行肾穿刺活检,诊断为抗中性粒细胞胞浆抗体相关性血管炎(antineutrophil cytoplasmic antibody-associated vasculitis,AAV),予以强的松+环磷酰胺(CTX)冲击治疗,缓解后行强的松+硫唑嘌呤(AZA)维持治疗.治疗期间MPO-ANCA于180. 04～238. 79 RU/ml之间上下波动,双眼眼红反复出现、视力进行性下降,并陆续出现胃部不适、胸闷、抬腿困难、下肢关节晨僵、右侧髋关节疼痛等肾外症状.2014年因右眼视力下降加重至北京某医院就诊,诊断"双眼角膜混浊、双眼翼状胬肉、血管性肾炎"行右眼穿透性角膜移植术.