Effect of menthol on ocular drug delivery

Background  

To assess how safe and effective it is to use menthol as a permeability enhancer in ophthalmic drug delivery systems.     

Pentacam系统检测角膜曲率和高度在圆锥角膜早期诊断中的应用

目的探讨Pentacam眼前节分析系统检测的角膜前后表面曲率和高度参数在临床期圆锥角膜、亚临床期圆锥角膜和正常角膜中的变化以及Pentacam眼前节分析系统在圆锥角膜早期诊断中的意义。设计诊断技术评价。研究对象临床期圆锥角膜组患者16例(16眼),亚临床期圆锥角膜组19例(19眼),有近视散光的患者29例(29眼)为正常对照组。方法应用Pen-tacam眼前节分析系统检测出临床期圆锥角膜组、亚临床期圆锥角膜组和正常对照组患者的角膜前后表面曲率和高度的12个参数。利用t检验和受试者工作特征曲线(ROC曲线)分析方法对各参数进行比较研究,利用偏最小二乘(PLS)方法构建临床期圆锥角膜和亚临床期圆锥角膜的早期诊断模型。主要指标角膜前后表面曲率和高度参数。结果角膜前后表面曲率和高度参数在临床期圆锥角膜组、亚临床期圆锥角膜组与正常对照组之间存在差异(P均<0.001)。ROC曲线分析结果显示临床期圆锥角膜组、亚临床期圆锥角膜组中各参数的曲线下面积(AUC)均接近于1,说明其诊断准确性较高,并且分别得出在临床期圆锥角膜和亚临床期圆锥角膜中较好参数的诊断界值:角膜前表面5 mm内在最佳配适球镜(BFS)上的最大高度(MaxAE5)为13.5μm和10μm,角膜后表面5 mm内在BFS上的最大高度(MaxPE5)为34.5μm和24.5μm。应用PLS方法构建了临床期和亚临床期圆锥角膜的早期诊断模型。结论 Pentacam眼前节分析系统检测的角膜前后表面曲率和高度参数对临床期圆锥角膜和亚临床期圆锥角膜的早期诊断有重要意义。     

自噬的分子机制及其在糖尿病视网膜病变中的作用

糖尿病视网膜病变（diabetic retinopathy,DR）是糖尿病微血管并发症之一,具有特征性的眼底表现,是临床上导致糖尿病患者失明的重要原因。近年来DR的发病率显著增长,严重威胁到糖尿病患者的身心健康,已成为关乎民众健康乃至国计民生的社会问题。DR发病机制复杂,多种因素如氧化应激、缺氧、炎症反应、内质网应激、多元醇途径等,均被证实与DR的发病密切相关。近年研究发现,自噬作为机体一种重要的防御机制,参与了DR的发生与发展,其病理过程涉及多种信号转导通路,与氧化应激、缺氧及新生血管形成尤为相关。因此,自噬与DR的关系成为临床研究的热点。     

Retrospective comparison of three-dimensional imaging sequences in the visualization of posterior fossa cranial nerves

PurposeTo compare efficancy of three-dimentional SPACE (sampling perfection with application-optimized contrasts using different flip-angle evolutions) and CISS (constructive interference in steady state) sequences in the imaging of the cisternal segments of cranial nerves V–XII.MethodsTemporal MRI scans from 50 patients (F:M ratio, 27:23; mean age, 44.5 ± 15.9 years) admitted to our hospital with vertigo, tinnitus, and hearing loss were retrospectively analyzed. All patients had both CISS and SPACE sequences. Quantitative analysis of SPACE and CISS sequences was performed by measuring the ventricle-to-parenchyma contrast-to-noise ratio (CNR). Qualitative analysis of differences in visualization capability, image quality, and severity of artifacts was also conducted. A score ranging ‘no artefact’ to ‘severe artefacts and unreadable’ was used for the assessment of artifacts and from ‘not visualized’ to ‘completely visualized’ for the assesment of image quality, respectively. The distribution of variables was controlled by the Kolmogorov–Smirnov test. Samples t-test and McNemar’s test were used to determine statistical significance.ResultsRates of visualization of posterior fossa cranial nerves in cases of complete visualization were as follows: nerve V (100% for both sequences), nerve VI (94% in SPACE, 86% in CISS sequences), nerves VII–VIII (100% for both sequences), IX–XI nerve complex (96%, 88%); nerve XII (58%, 46%) (p < 0.05). SPACE sequences showed fewer artifacts than CISS sequences (p < 0.002).     

Comparison of posterior capsule opacification in rabbit eyes receiving different administrations of rapamycin

Background

Posterior capsule opacification (PCO) is a common complication after cataract surgery. The purpose of this study was to determine the effects of three administering ways of rapamycin (RAPA) on the formation of PCO in rabbit eyes for 12 weeks.

Methods

Eighty rabbits were divided into four groups, according to the different administrations of RAPA which they received. These were: (1) the control group, (2) the irrigation-treated group — 5 ng/ml intraoperative RAPA irrigation solution, (3) the eye-drop-treated group — 2 mg/ml RAPA eye drops, and (4) the IOL-treated group — RAPA–poly(lactic-co-glycolic) acid (PLGA) loaded on the surface of intraocular lens (IOLs) (RAPA-PLGA-IOLs). All right eyes were treated with lens extraction plus IOL implantation, receiving relative administrations of RAPA. RAPA concentrations in the aqueous humour were determined by high performance of liquid chromatography (HPLC). The anterior chamber (AC) response was observed through slit-lamp biomicroscopy. After 12 weeks, the degree of PCO was determined by clinical evaluation. The histological sections, immunohistochemistry expression of proliferating cell nuclear antigen (PCNA) in the lens capsule were conducted.

Results

In the early period, AC response for both experimental and control eyes were similar. In the IOL-treated group, RAPA reached its peak at 25.68?±?0.74 μg/ml on the 4th day, and it was detectable until 8 weeks afterwards. However, in the other groups, RAPA could not be detected all the time. Compared with other groups, in the IOL-treated group, PCO was greatly alleviated; only a few layers of the lens epithelial cells (LECs) and a little proliferative material around the posterior capsules, and a significantly weak expression of PCNA in the nuclei of LECs. By contrast, there was no significant statistical difference in eye-drop-treated or irrigation-treated eyes and control eyes respectively.

Conclusions

Intraocular RAPA-PLGA-IOL was a promising, effective, and safe administration to prevent PCO compared with other methods in the rabbit PCO model.     

Polylactide-glycoli acid and rapamycin coating intraocular lens prevent posterior capsular opacification in rabbit eyes

Objectives  Posterior capsular opacification (PCO) is caused by the proliferation and migration of residual lens epithelium cells (LECs) after extracapsular cataract extraction (ECCE). Rapamcin (RAPA) is known to be a potent immunosuppressive drug with anti-inflammatory and anti-proliferative effects. The aim of this study was to investigate the safety and efficacy of rapamycin sustained release from modified intraocular lens (IOLs) in the prevention of PCO in rabbits. Methods  Three types of IOLs were used, including the original IOL without modification, IOL with polylactide-glycoli acid (PLGA) coating (PLGA-IOL), and RAPA-loaded PLGA-IOL (RAPA-PLGA-IOL). Sixty New Zealand albino rabbits undergoing phacoemulsification in left eyes were randomly and equally divided into three groups. Group A was implanted with the original IOLs, group B was implanted with the PLGA-IOLs, and group C was implanted with the RAPA-PLGA-IOLs. All of the 60 treated left eyes were examined by a slit-lamp microscope. The concentrations of RAPA in the aqueous humor and blood were determined by high-performance liquid chromatography (HPLC), indicating an vivo release of drug from the polymer carrier. Anterior segment tissue was histologically examined, and wet posterior capsules were weighed. Six months after intervention the PCO was graded. Results  The mean concentrations of RAPA in the aqueous humor from group C at 2 h, 1 days, 3 days, and 7 days after operation were 12.81 ± 1.27 μg/ml, 14.57 ± 0.99 μg/ml, 6.39 ± 0.95 μg/ml, and 1.10 ± 0.32 μg /ml respectively. The concentrations of RAPA in blood were undetectable. During the early days after the operation, the reactions of the anterior chamber from groups A and B were more severe than from group C. Our findings showed that the initial appearance of PCO in group C was much later than in the other two groups. The wet posterior capsules were weighed to be 0.3735 ± 0.0943 g (group A), 0.3754 ± 0.1093 g (group B), and 0.0432 ± 0.0089 g (group C). Histological observation showed a similar phenomenon, that there was remarkably less accumulation of lens materials on the posterior capsules in group C than in the other two groups. Conclusion  Our findings suggest that the designed RAPA-PLGA-IOL effectively prevented formation and development of PCO for a relatively long duration.     

Ocular pharmacokinetic study on baicalin in lens of rabbits following intragastric administration

Purpose  

This paper is to study the pharmacokinetic features of baicalin in lens through observing baicalin’s concentration changes in lens of rabbits following intragastric administration.     

Down-regulation of inducible co-stimulator (ICOS) by intravitreal injection of small interfering RNA (siRNA) plasmid suppresses ongoing experimental autoimmune uveoretinitis in rats

Background  RNA interference (RNAi) is now being exploited as a powerful tool for gene knockdown. Recently, we had shown that inducible co-stimulator (ICOS) was up-regulated in experimental autoimmune uveoretinitis (EAU). The aim of this study was to investigate whether intravitreal injection of small interfering RNA (siRNA) plasmid, targeting ICOS, suppresses the ongoing experimental autoimmune uveoretinitis (EAU) in rats. Methods  Oligonucleotide targeting ICOS was cloned into linearized pRNAT-U6.1/Neo eukaryotic expression vector to construct the recombinant plasmid (pRNAT-U6.1/Neo-ICOS). After transfecting activated rat T cells with the recombinant plasmid, ICOS mRNA and protein expression levels were determined by real-time RT-PCR and Western blot analysis respectively. Rats were immunized with IRBP R16 peptide emulsified in complete Freund’s adjuvant (CFA) and given an intravitreal injection of pRNAT-U6.1/Neo-ICOS on day 6 after immunization. After 13days of immunization, the ICOS protein expression and CD4 ⁺ ICOS ⁺ T cells were identified in retinae through Western blot analysis and flow cytometry respectively. Intraocular inflammation was assessed by the scores of the clinical and histological appearances. Delayed-type hypersensitivity (DTH) and lymphocyte proliferation were detected to evaluate the systemic effect of intravitreal injection of pRNAT-U6.1/Neo-ICOS. Result  The recombinant plasmid (pRNAT-U6.1/Neo-ICOS) for the ICOS siRNA was successfully constructed. In vitro studies using the recombinant plasmid has showed the down-regulation of ICOS gene expression both at the mRNA and protein levels. Clinical and pathological scores showed that ocular inflammation of pRNAT-U6.1/Neo-ICOS-treated eyes was markedly less than that of vehicle-treated eyes. The expression of ICOS protein and the amount of CD4 ⁺ ICOS ⁺ T cells in retinae significantly decreased by intravitreal injection of the recombinant plasmid, whereas delayed-type hypersensitivity response and lymphocyte proliferation were not impaired in rats treated with the recombinant plasmid. Conclusion  Intravitreal injection of siRNA plasmid targeting ICOS effectively down-regulated the expression of ICOS, and was highly effective in suppressing the ongoing process of EAU without any side-effects on systemic cellular immunity. Yongsheng Hou and Lin Xing contributed equally to this study