Tumor necrosis factor-alpha (TNF-α)-mediated in vitro human retinal pigment epithelial (RPE) cell migration mainly requires Akt/mTOR complex 1 (mTORC1), but not mTOR complex 2 (mTORC2) signaling

When rhegmatogenous retinal detachment occurs, tumor necrosis factor-alpha (TNF-α) among other cytokines leaks into the subretinal space, induces resident retinal pigment epithelial (RPE) cells to migrate, which is the initial step of proliferative vitreoretinopathy (PVR). In the current study, we aim to understand how this is regulated by focusing the cellular mechanisms involved. Here we identified an Akt/Tuberous sclerosis protein 2 (TSC2)/mTOR complex1 (mTORC1) signaling pathway after TNF-α treatment to mediate RPE cell migration. Suppression of mTORC1 activation, either by its inhibitor rapamycin, or by activation of its suppressor AMP activated protein kinase (AMPK), inhibited TNF-α-mediated RPE cell migration, while RNA interference (RNAi)-mediated knocking-down of SIN1 or Rictor, two key components of mTOR complex 2 (mTORC2), had no significant effect on TNF-α-induced RPE cell migration. Our data provide initial evidence that TNF-α-mediated in vitro RPE cell migration mainly requires Akt/mTORC1, but not mTORC2 signaling. The results of this study may lead to indentify novel signaling targets against PVR.     

Is lipoprotein(A) a risk factor for atherosclerosis of the retinal arteries?

Elevated plasma Lp(a) has been linked to development of coronary artery disease (CAD). There is no data about plasma Lp(a) and atherosclerosis of the retinal arteries. Therefore the purpose of this study was to assess the risk of retinal vessels atherosclerosis conferred by elevated plasma Lp(a) levels in 73 adult males. The results were compared with those in 45 matched apparently healthy males with no retinal vessel changes. The atherosclerotic changes of the retinal vessels were determined by direct ophthalmoscopy and graded (1-4) according to Scheie. Plasma levels of Lp(a) were measured by radial immunodiffusion. The results were compared using chi-square test. Although a very weak correlation between plasma Lp(a) levels and the incidence of retinal atherosclerosis was found, no significant association between the degree of atherosclerotic changes and plasma Lp(a) levels could be proven. Thus it could be concluded that plasma Lp(a) level is not a significant risk factor for atherosclerosis of the retinal arteries.     

Does glaucoma medication influence the diameter of the retinal arteriole in the human eye? (A pilot study using the retinal vessel analyser)

PURPOSE: To investigate the potential in vivo influence of different topical glaucoma medications on the diameter of the retinal arterioles of healthy volunteers and glaucoma patients. METHODS: The diameter of one pre-selected retinal arteriole per eye was measured using the Retinal Vessel Analyser (RVA), an instrument developed for non-invasive clinical measurement of the diameter of the main retinal vessels. The instrument contains a video system, and the integrated software recognises the boundaries of the retinal vessels by detecting their light-transmission profile. The vessel diameter (in arbitrary units) is plotted against time (seconds) on a separate display screen. In Study I the vessel diameter was measured in 12 eyes of six healthy volunteers (age 21-26 years, mean age 24.0 years) on six occasions each separated by 14 days. In a double-masked fashion, each subject's right eye was treated with one of 5 glaucoma medications (brinzolamide 1%, timolol 0.5%, betaxolol 0.5%, brimonidine 0.2% or latanoprost 0.005%) and the left eye always received balanced salt solution. In Study II, one randomly selected eye of 16 patients (age 50-79 years, mean age 65.2 years) suffering from primary open-angle glaucoma controlled with topical monotherapy was investigated, in an unmasked fashion. Four patients were on betaxolol 0.5% treatment, six subjects were receiving non-selective topical beta receptor blockers and six subjects were being treated with once daily latanoprost 0.005%. RESULTS: The coefficient of variation for the arteriole diameter in the healthy volunteers was less than 12% in each case. No significant post-treatment change of the diameter of the pre-selected arteriole was found for any topical medication investigated, either in the healthy volunteers (Study I) or in the patients suffering from glaucoma (Study II) (p>0.05, paired t-test). In addition, in Study I no difference was observed in the alteration of the arteriole diameter between the baseline and the hour 2 measurements when the values from the drug-treated and placebo treated eyes were compared (p>0.05, two-way ANOVA). CONCLUSION: In the present investigations it was not possible to detect any statistically meaningful change of the arteriole diameter at two hours after the instillation of any of several topical antiglaucoma drugs widely used in clinical practice. Further investigations are necessary to clarify whether the lack of observed change is due to the lack of retinal vascular effects of the drugs investigated, or is due to an inability of the RVA instrument in practice to detect alterations between time-points separated by several hours.     

植物新陈代谢(2)

(续 2 0 0 3年第 38卷第 7期第 4 5页 )3　能力训练3.1　实验设计 ,不仅有助于学生掌握基本概念和原理 ,更有助于学生掌握科学的研究方法 ,培养学生的创造性思维 ,培养学生应用所学知识综合解决问题的能力 ,是培养学生综合素质的有效手段。例题 1:设计一个实验 ,验证缺硼会影响油菜的结实率。 (答案 :略 )例题 2 :设计一个实验测定洋葱表皮细胞细胞液的质量分数 ?(利用质壁分离实验原理可测定细胞的质量分数 ,答案 :略 )3.2　研究影响酶作用因素实验方法　　研究某一因素对酶促反应速度的影响时 ,应在保持其他因素不变的情况下 ,单独改变研…