埃罗替尼对小鼠角膜上皮组织病理学及超微结构的影响

目的 探讨埃罗替尼对小鼠角膜上皮组织引起的组织病理学及超微结构改变的影响.方法 30只雄性6～8周龄BALB/c小鼠,随机分为对照组(12只)和实验组(12只),6只不作处理为空白对照.实验组使用20 μmol·L-1埃罗替尼液滴眼,对照组采用PBS滴眼,每天4次.分别在干预后1d、7d、14 d对各组小鼠进行荧光素钠(fluorescent,FL)染色及评分.干预后14 d取小鼠眼球,光学显微镜及电子显微镜下观察角膜上皮及细胞的结构变化.提取角膜蛋白进行Western Blot检测.结果 干预前,实验组和对照组FL评分比较差异无统计学意义(P＞0.05).在干预后1d、7d、14 d,实验组FL评分较干预前明显升高,差异均有统计学意义(均为P＜0.05),而对照组FL评分与干预前无明显改变,差异均无统计学意义(均为P＞0.05);两组间FL评分在干预后1d相比,差异无统计学意义(P＞0.05);两组间FL评分在干预后7d、14 d相比,差异均有统计学意义(均为P＜0.05).实验组小鼠角膜上皮细胞排列紊乱,层数增加;电镜下见角膜上皮表层细胞形态不规则、脱落,微绒毛减少、消失;表层上皮细胞的桥粒、半桥粒连接数目明显减少.实验组角膜表皮生长因子受体表达明显发生变化,两组表皮生长因子受体比较差异有统计学意义(P＜0.05).结论 埃罗替尼会引起小鼠角膜上皮的组织结构及细胞超微结构损坏.其机制可能是通过抑制表皮生长因子受体的活化来影响角膜上皮的.     

厄洛替尼对非增生型糖尿病视网膜病变的治疗作用及机制的实验研究

目的探讨表皮生长因子受体(EGFR)抑制剂厄洛替尼对非增生型糖尿病视网膜病变(NPDR)的治疗作用及机制。方法实验研究。人视网膜Müller细胞(RMC)为Moorfields眼科医院和伦敦大学学院眼科学研究所-Müller 1(MIO-M1)细胞。将MIO-M1细胞分为正常对照、高渗、高糖、高糖+二甲基亚砜(DMSO)、高糖+厄洛替尼 0.5 mmol/L、高糖+厄洛替尼 1 mmol/L和高糖+厄洛替尼 2 mmol/L组。5-乙炔-2′-脱氧尿苷(EdU)掺入实验检测厄洛替尼对高糖条件下MIO-M1细胞增殖的影响;Western印迹检测厄洛替尼对高糖条件下MIO-M1细胞活化标记胶质纤维酸性蛋白(GFAP)和谷氨酰胺合成酶(GS)蛋白水平的影响。Western印迹检测厄洛替尼对高糖条件下RMC中p75神经生长因子受体(p75NTR)、波形蛋白和细胞视黄醛结合蛋白(CRALBP)蛋白水平的影响。将MIO-M1细胞分为正常对照、高糖、高糖+DMSO和高糖+厄洛替尼1 mmol/L组, 采用细胞免疫荧光染色检测厄洛替尼对高糖条件下EGFR核转位的影响;免疫共沉淀检测厄洛替尼对高糖条件下...     

持续性角膜上皮缺损的治疗进展

持续性角膜上皮缺损(PED/PCEDs)是指角膜损伤后10～14d内,在接受了相应治疗后,角膜也未能迅速重新形成上皮并闭合而导致的一种角膜疾病。角膜上皮的破坏和基质层的损伤容易使眼部受到感染、发生基质溃疡、穿孔、瘢痕,甚至丧失视力。就目前而言,临床医生对PED的治疗仍然面临相当大的挑战。标准的治疗方法包括配戴绷带隐形眼镜和使用人工泪液治疗,而新开发的药物则可以通过促进各类生长因子的生成使角膜重新形成上皮,进一步配合相应外科手术为角膜提供神经支配,以此达到治疗的效果。此外,确诊PED后应尽早接受治疗,以避免继发性并发症。本文就PED的流行病学、病因学、诊断与临床表现、治疗方法及预后进行综述。     

组织粘合剂粘合羊膜手术在眼表重建术中的应用

目的:评价组织粘合剂粘合羊膜手术在眼表重建术中的疗效.方法:对16例17眼由于各种原因造成的角膜上皮持久不愈合的患者实施羊膜手术,术中用组织粘合剂固定羊膜.其中Ⅳ度以下眼化学烧伤4例5眼,外伤或异物剔除术后持续性角膜溃疡4例4眼,局限性蚕蚀性角膜溃疡3例3眼,神经麻痹性角膜溃疡和暴露性角膜溃疡各2例2眼,绝对期青光眼合并大泡性角膜病变1例1眼.全部患者在术前给予常规的药物治疗,术后予加压包扎、局部抗炎等处理.随访2～12 mo,观察视力及局部反应、角膜上皮的生长情况、羊膜的贴附情况等.结果:手术后88%的患眼上皮缺损愈合,愈合时间为9～48(26.7±7.8)d,羊膜贴附的时间约为1mo,83%的患眼视力有不同程度的提高.结论:对于有角膜缘干细胞残存的眼表,组织粘合剂粘合羊膜手术可以恢复眼表的完整性,有效地防止持续性角膜上皮缺损,改善患者局部刺激症状.     

The Role of Multisystem Disease in Composition of Autologous Serum tears and ocular surface symptom improvement

PurposeAutologous serum tears (AST) contain growth factors and vitamins similar to those in healthy tears and are an effective treatment option for ocular surface disease. This study determined the differences in composition of AST in patients with systemic diseases versus patients with localized ocular surface diseases and the effects on ocular surface symptom improvement.MethodAn observational study was performed on 53 patients with either systemic diseases (Group I) or localized ocular surface diseases (Group II) who were prescribed AST. Concentrations of epidermal growth factor (EGF), interleukin 8 (IL-8), fibronectin, vitamin A, and tumor necrosis factor-α (TNF-α) were determined through ELISA assays from patients in both groups. The Ocular Surface Disease Index (OSDI) scores were calculated prior to and 6 weeks after initiation of treatment with AST for new patients.ResultsThe average concentration of EGF in Group I (29.39 pg/ml ± 52.85 pg/ml) was significantly lower than in Group II (88.04 pg/ml ±113.75 pg/ml) (p < 0.05). Levels of fibronectin, IL-8, and vitamin A were similar in both groups. There was a 24% reduction in OSDI score 6 weeks after initiation in Group I compared to a 36% reduction reported in Group II (p = 0.065). The OSDI score was reduced significantly after the treatment in all subjects (p = 0.002).ConclusionSerum tears are a promising therapy for management of ocular surface disease and associated symptoms. The differences between levels of EGF in patients with localized ocular surface disease and systemic inflammatory disease may account for differences in therapeutic outcome.     

Persistent epithelial defects and ulcers in repeated corneal transplantation: incidence, causative agents, predisposing factors and treatment outcomes

PURPOSE: To evaluate the occurrence, predisposing factors and outcome of persistent epithelial defects and ulcers complicating repeated corneal transplants. METHODS: The charts of all the patients that underwent repeated corneal transplantation between 1985 and 1998 were retrospectively reviewed for the presence of persistent epithelial defects and ulcers. The repeated corneal transplantation group included 122 regrafts performed in 80 patients. The follow-up period was at least 6 months after the last transplantation (average 31.5 months). RESULTS: Persistent epithelial defects and/or corneal ulcers affected 31 of the 122 regrafts (25.4%) in 23 patients (29%). Of the repeated grafts, 18 had persistent epithelial defects, five had ulcers and eight had persistent epithelial defects complicated by ulcers. Nine of the 31 regrafts (29%) that developed persistent epithelial defects or ulcers had positive bacterial cultures. The survival proportion was similar for regrafts with persistent epithelial defects and with ulcers (p = 0.859), but lower in the regrafted group with persistent epithelial defects and ulcers compared with the entire repeated corneal transplantation group (p < 0.001). In ten patients (43%), one or several eyelid abnormalities and ocular surface disorders were identified. They were more common in repeated keratoplasties with epithelial defects or ulcers than in repeated keratoplasties without them (p < 0.0001). Persistent epithelial defects developed more commonly after cyclocryotherapy for refractory glaucoma (p = 0.001). CONCLUSIONS: Ulcers and persistent epithelial defects are common in repeated corneal transplantation and are associated with poor graft survival. Predisposing factors should be disclosed before regrafting and promptly treated.     

表皮生长因子在白内障超声乳化术后眼表损伤修复过程中的作用

背景 随着白内障超声乳化联合后房型人工晶状体(IOL)植入术治疗年龄相关性白内障的广泛应用,部分患者术后感到明显的烧灼感、异物感,该手术对患者眼表的损伤及影响多有报道. 目的 观察重组人表皮生长因子(rhEGF)对年龄相关性白内障患者行白内障超声乳化联合IOL植入术后眼表损伤的修复作用.方法 采用前瞻性研究方法.选择确诊为年龄相关性白内障并行白内障超声乳化联合IOL植入术的患者89例120眼,依据术后第1天给予滴眼液的不同分为rhEGF组、玻璃酸钠组和空白对照组,每组40眼.各组间术前角膜荧光素染色、泪膜破裂时间(BUT)及泪液分泌(Schirmer Ⅰ)试验结果差异均无统计学意义(均P＞0.05).各组基础用药为质量分数0.3％氧氟沙星眼膏和妥布霉素地塞米松滴眼液,持续2周.术后第1天rhEGF组和玻璃酸钠组分别给予rhEGF滴眼液、玻璃酸钠滴眼液点眼,每日4次,持续4周.患者分别于术前1d及术后1d、1周、2周和1个月时行角膜荧光素染色、BUT及Schirmer Ⅰ试验检测,并进行比较分析.结果 3个组间人口基线特征差异均无统计学意义(F年龄=3.740,x2性别=0.615,P＞0.05),术前1d眼表检查差异亦无统计学意义(角膜荧光素染色评分:F=0.247,P＞0.05:BUT:F=0.579,P＞0.05;Schirmer Ⅰ试验:F=0.475,P＞0.05).随着术后时间的延长,各组内角膜荧光素染色评分、Schirmer Ⅰ试验结果均出现先升高后下降的趋势,BUT出现先缩短后延长的趋势,3个组术前1d,术后1d、1周、2周、1个月时角膜荧光素染色评分值、BUT、Schirmer Ⅰ试验结果各时间点间差异均有统计学意义(F时间=6.754、6.233、6.079,P＜0.01);3个组间差异亦有统计学意义( F分组=4.953、4.071、4.511,P＜0.05).rhEGF组术后2周和术后1个月角膜荧光素染色评分明显低于玻璃酸钠组(P=0.039、0.014),1个月时恢复至术前水平(P=0.137).rhEGF组术后1周和2周时BUT均明显高于玻璃酸钠组(P=0.019、0.007),于2周时恢复至术前水平(P=1.009).rhEGF组在术后1周、2周、1个月时Schirmer Ⅰ试验值均明显低于玻璃酸钠组(P=0.022、0.003、0.019),于2周时恢复至术前水平(P=0.052).结论 rhEGF可明显促进白内障超声乳化术后眼表损伤的修复.     

The role of nitric oxide in ocular surface physiology and pathophysiology

Nitric oxide (NO) has a wide array of biological functions including the regulation of vascular tone, neurotransmission, immunomodulation, stimulation of proinflammatory cytokine expression and antimicrobial action. These functions may depend on the type of isoform that is responsible for the synthesis of NO. NO is found in various ocular tissues playing a pivotal role in physiological mechanisms, namely regulating vascular tone in the uvea, retinal blood circulation, aqueous humor dynamics, neurotransmission and phototransduction in retinal layers. Unregulated production of NO in ocular tissues may result in production of toxic superoxide free radicals that participate in ocular diseases such as endotoxin-induced uveitis, ischemic proliferative retinopathy and neurotoxicity of optic nerve head in glaucoma. However, the role of NO on the ocular surface in mediating physiology and pathophysiological processes is not fully understood. Moreover, methods used to measure levels of NO in the biological samples of the ocular surface are not well established due to its rapid oxidation. The purpose of this review is to highlight the role of NO in the physiology and pathophysiology of ocular surface and propose suitable techniques to measure NO levels in ocular surface tissues and tears. This will improve the understanding of NO's role in ocular surface biology and the development of new NO-based therapies to treat various ocular surface diseases. Further, this review summarizes the biochemistry underpinning NO's antimicrobial action.     

Cataract surgery in patients with ocular surface disease: An update in clinical diagnosis and treatment

In this article we review essentials of diagnosis and management of ocular surface disease in patients who undergo cataract surgery. It is clearly shown that dry eye disease worsens following the cataract surgery in patients with prior history of ocular surface disease, Also new cases of dry eye might appear. Current strategies for the timely diagnosis and proper management of dry eye syndrome in the face of cataract surgery patients are mainly emphasized. To achieve the best outcome in cataract surgery, a healthy ocular surface is crucial. While ocular surface preparation is indispensable in patients with established ocular surface disease, it is also helpful in those with minimal signs or symptoms of surface disease. The current approach begins with early diagnosis and drastic management of ocular surface disease before cataract surgery using a stepwise regimen customized to each patient and disease severity. These measures are continued throughout and after the surgery.     

Factors affecting recurrence after surgical treatment in cases with ocular surface squamous neoplasia

AIM: To evaluate the risk factors leading to recurrence in patients with ocular surface squamous neoplasia (OSSN) METHODS: The records of 112 patients with OSSN who underwent treatment and follow-up between February 1999 and August 2018 were reviewed retrospectively. RESULTS: Totally 67 patients (59.8%) were male and 45 patients (40.2%) were female. The mean age at presentation was 63.7y (range 22-87y). Partial lamellar scleroconjunctivectomy (PLSC) was performed in 105 (93.7%) cases and enucleation was performed in 7 (6.3%) cases due to bulbus invasion as the first step treatment. Treatments used in addition to PLSC included cryotherapy in 78 eyes (74.3%), alcohol epitheliectomy in 57 eyes (54.3%) for presence of corneal involvement, and amniotic membrane transplantation in 17 eyes (16.2%) for ocular surface reconstruction. Topical mitomycin C was used in 10 patients (9.5%) and strontium-90 (Str-90) treatment in 4 (3.8%) patients because surgical margins were tumor positive at the histopathological examination. Postoperative histopathologic diagnoses were squamous cell carcinoma (52 cases), carcinoma in situ (44 cases), moderate conjunctival intraepithelial neoplasia (11 cases), and mild conjunctiva intraepithelial neoplasia (5 cases). At a mean follow-up of 20.1mo, tumor recurrence was observed in 21 (18.8%) cases. The rate of recurrence was found to be lower in cases that underwent supplemental cryotherapy compared to those that did not (P<0.001). There was no metastasis in any case. CONCLUSION: In our series, the recurrence rate is 18.8% and overall globe salvage rate is 90.2% for OSSN at relatively short-term follow-up.     

生存素(Survivin)抑制剂YM155对视网膜色素上皮细胞活力和迁徙能力的影响

目的　探讨生存素(Survivin)抑制剂YM155对视网膜色素上皮细胞活力和迁徙能力的影响。方法　将ARPE-19细胞分为对照组（不作任何处理）,10 nmol?L^-1、20 nmol?L^-1、50 nmol?L^-1 YM155组（用相应浓度YM155处理细胞24 h）,MTT检测各组细胞活力,Western blot检测各组细胞表皮生长因子受体（EGFR）、AKT、Survivin蛋白的表达情况;采用细胞迁徙实验和免疫荧光染色实验检测对照组与20 nmol?L^-1 YM155组细胞迁徙能力和EGFR表达情况。结果　MTT检测结果显示,与对照组相比,10 nmol?L^-1、20 nmol?L^-1和50 nmol?L^-1YM155组ARPE-19细胞的相对细胞活力平均降低约42.3%、55.6%、73.0%,差异均有统计学意义(均为P<0.01)。使用20 nmol?L^-1YM155处理ARPE-19细胞24 h会降低细胞迁徙能力。YM155处理细胞24 h后,10 nmol?L^-1 YM155组细胞EGFR和AKT蛋白表达,与对照组相比无明显差异（均为P<0.05）,但Survivin蛋白表达下调（P<0.05）;20 nmol?L^-1YM155组细胞AKT蛋白表达,与对照组相比亦无明显差异（P>0.05）,EGFR和Survivin蛋白表达均下调（均为P<0.05）;50 nmol?L^-1组细胞EGFR、AKT和Survivin三种蛋白表达均下调,与对照组相比差异均有统计学意义(均为P<0.05)。免疫荧光染色检测结果显示,对照组ARPE-19细胞EGFR均匀表达于细胞膜,20 nmol?L^-1YM155组表达于细胞膜的EGFR被内吞转移到细胞质内,在细胞核周围呈颗粒状分布;YM155可以诱导细胞骨架损害、F-肌动蛋白纤维排列紊乱,细胞核增大。结论　YM155能抑制ARPE-19细胞活力和迁徙能力,YM155对视网膜色素上皮细胞活力和迁徙能力的影响与Survivin、EGFR和AKT的蛋白表达下调有关。     

Exploring topical anti-glaucoma medication effects on the ocular surface in the context of the current understanding of dry eye

Purpose

To assess tear film parameters, ocular surface characteristics, and dry eye symptomology in patients receiving topical anti-glaucoma medications.

Long-term outcome of using Prosthetic Replacement of Ocular Surface Ecosystem (PROSE) as a drug delivery system for bevacizumab in the treatment of corneal neovascularization

Purpose

To report the long-term outcome of Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) for delivery of bevacizumab in the treatment of corneal neovascularization (KNV).

Effects of estrogen replacement therapy on apoptosis and vascular endothelial growth factor expression in ocular surface epithelial cells: An experimental study

AIM: To investigate the effects of estrogen replacement therapy (ERT) on apoptosis and vascular endothelial growth factor (VEGF) expression in ocular surface in an experimental rat model. METHODS: Forty female, Wistar rats were randomized in 4 groups in the study. Subcutaneous ERT (17β-estradiol, 10μg/kg/day) was administered to the first group without ovariectomy and to the second group with ovariectomy for three months. Third group had only ovariectomy and fourth group had sham operation. All rats were sacrificed in estrous cycles determined by vaginal smear test and their right eyes were enucleated at the end of the third month. Enucleated eyes were analyzed by immunohistochemical method for expressions of caspase-3, bcl-2, VEGF and TUNEL assay. RESULTS: Caspase-3 expression of conjunctival epithelium was significantly higher in group 3 than group 1 (P=0.005), and group 2 (P=0.007). TUNEL score of conjunctival epithelium was significantly higher in group 3 than group1 (P=0.006). TUNEL score of corneal epithelium was significantly higher in group 3 than group 2 (P=0.012), and group 4 (P=0.002). There was no significant difference between groups in that bcl-2 and VEGF expressions. CONCLUSION: We determined increased apoptosis in ocular surface epithelial cells in ovariectomized rats. ERT and endogen estrogen decreased the apoptosis, and did not result in difference in VEGF expression between the groups. Estrogen may be beneficial for the treatment of apoptosis-mediated ocular surface disorders such as dry eye. Further studies are needed on this subject for a better understanding of the role of estrogen and to provide a new insight for treatment and prevention of apoptosis-mediated ocular surface disorders.