设为首页         
  
首 页 学术动态   最新资讯   会议专题 学术幻灯 专家访谈 精彩视频 病例讨论 循证指南 积分商城 名家讲堂
当前位置:眼科首页>(ARVO)美国眼科和视觉研究协会年会>正文
[ARVO2013]警惕:眼部弓形虫病
——ARVO候任主席Justine R. Smith教授专访

防盲与流行病  作者:  J.R.Smith  2013/7/9 16:34:00
国际眼科时讯版权所有,谢绝任何形式转载,侵犯版权者必予法律追究。
内容概要:国际眼科时讯: Dr. Smith,您目前正在致力于眼弓行虫病的研究,那么,能否请您简要地描述下你的研究及其原因?

  <International Ophthalmology Times>: Dr. Smith, you are currently working on ocular toxoplasmosis. That is what you are primarily working on these days. Can you give us a thumbnail sketch on what you are studying and why?
国际眼科时讯: Dr. Smith,您目前正在致力于眼弓行虫病的研究,那么,能否请您简要地描述下你的研究及其原因?
Dr. Smith: Yea, toxoplasmosis is a disease that is very common. About one third of the world’s population is infected with protozoan toxoplasmosis gondii which is a parasite. Most of the work that is done on this parasite is done in tissue culture and in animal models. The primary model that is used to study this parasite is the mouse model but the big problem with this is that the mouse model and the human model react very differently to the parasite ultimately. So, if you infect a mouse with toxoplasmosis, ultimately it dies. A third of the world’s population has the parasite. Obviously, we have a very different interaction. We survive. Although we are at risk of recurrent infection a little bit like you would be with the cold sore virus. So the problem is that if the work is being done in the mouse, how translatable is it to humans? So our group prides our self with human tissue in order to better understand the mechanism of the disease as it occurs in the human host. There are very simple questions concerning the parasite that just have not been addressed. For example, we know that the parasite is typically ingested but how does it get from the blood stream to the eye? Once it is in the eye can it move around in the eye? Which cells does it infect? How is it ingested? How does the body react to it? All these questions are questions that really haven’t been addressed in a human system. So that’s what we do. And some of the nice stuff that we do recently has been able to sort of answer these questions. So we have been able to show recently that the parasite can probably move independently through the blood vessel wall in the retina to infect the retina. So, ocular toxoplasmosis is typically based in the retina. We think that there actually may be something special about the retina blood vessel wall that makes the parasite more likely to infect the retina than other tissues in the eye and indeed the body. So the parasite, when it infects the human host, has a propensity to infect the central nervous system including the retina. A part of the reason probably has to do with the fact that that part of the body does not have the ability to remove the parasite as easily because of immune privilege but we think that part of it is also a special relationship between the parasite and the blood vessel wall at a molecular level. So the blood vessel wall by cells called endothelium cells and endothelium cells line the blood vessel walls throughout the body. On the face of it, you would think that, being continuous, that they would all be the same but depending on the tissue you are talking about or the kind of blood vessel artery you are talking about the molecular makeup of the tissue could be very different throughout the body. And that could be very important in tissue specific diseases. Why does the disease, for example, occur in the retina and not in the liver? And so our group has spent some years trying to figure out what is special about the endothelium cells of the retina as opposed to endothelium cells elsewhere. And we typically profile the retina endothelium cells against the choroid endothelium cells. And you know the choroid is adjacent to the retina and so the choroid is probably the closest tissue you can get to profile the retina tissue blood vessels if you don’t want to bring donors into the equation. The great thing about the eye is that you can obtain an eye from a human cadaver and you can compare the endothelium cells from the retina and the endothelium cells from another part of the eye without having to take into account the differences that are just differences between individuals. For example, if we took your retinal endothelium cells and my choroid endothelium cells they would be different because we are different people. If you want to understand to really understand what is special about the retina endothelium cells at the molecular level we would need to take my retina endothelium cells and compare it to endothelium cells somewhere else in my body not your body because if we compare my endothelium cells to your choroid cells they are going to be different. In that case, the difference could not be in the choroid cells themselves but from the fact that you and I are different. So we have spent a lot of time working on that and we have a very nice profile now, at the molecular level, of retina endothelium cells. So, we believe that there is also an aspect of the retinal endothelium cells that determines the fact that the parasite likes to get into the retina. And we have been able to show that the endothelium cells of the retina have very high levels of an adhesion molecule called  vascular cellular adhesion molecule-1 (VCAM-1) and the parasite can use this particular adhesion molecule to move into the retina. So when you try and set up the system to mimic parasite migration across the blood stream into the retina, which you can do in a tissue culture system, and you use retinal endothelium cells to populate that system and you compare it with the same system populated with the choroid endothelium cells you’ve got VCAM-1 in the population in the retinal system and you prevent parasite migration but you do not see that in the population in the choroid system. We’ve been able to show that the parasite is probably able to move on its own through the retinal endothelium and that there are probably molecules on the surface of that system to facilitate that movement.  And this is part of the reason why the parasite is lodged in the retina. Therefore, as mentioned before, a third of the world’s population is infected with the parasite but by far the most common, clinical manifestation of toxoplasmosis is infection in the retina which is called ocular toxoplasmosis.  So that is by far the most common manifestation of this disease. So, if you look in the literature at this disease from the parasitological community you would get the impression that is really only a problem for those who are immune compromised such as neonatal infection before birth or patients who have autoimmune deficiency disorders that could be caused by an infection such as HIV/ AIDS. But actually if you go to the ophthalmology literature you will find that actually the biggest group of patients with toxoplasmosis are completely healthy adults. So this is actually a very important problem and also a world-wide problem. If you look at developing countries, for example Brazil, ocular toxoplasmosis is the leading cause of blindness in children. It is amazing that there are so few people working on this disease. Actually, I have never really understood that. There is a big parasitological community that works on this disease but outside this community there are not that many working on this disease, trying to understand the clinical basis as it affects humans. So there is a large parasitology group. It is not as big as the community that works on malaria but there is a dearth of people working on the parasite as it relates to the eye and human eye disease.
Dr. Smith:好的,弓行虫是一种非常常见的疾病。现在全球大约1/3的人口感染原生动物刚地弓形虫(一种寄生虫)。大部分的该寄生虫研究工作是有关组织培养和动物模型的。该研究用的模型是小鼠模型,此模型有一个大的问题:终究地,小鼠模型和人类模型对该寄生虫的反应会存在大大的不同。因此,如果你用弓形虫转染一小鼠,那么它最终会死亡。世界1/3的人口携带此寄生虫。那么明显地,我们有不同的感染反应。我们生存下来了。尽管我们面临着复发感染的可能性,但是此可能性与感染唇庖疹病毒的情况有些相似。因此问题在于:如果我们正在小鼠身上做研究,那么如何在人身上达到同步呢?故我们团队有一值得骄傲的创举:当人类感染了该寄生虫时,我们用人类组织来更好地研究该疾病的发病机制。接下来我们探讨下有关该寄生虫的尚未被提及的一些简单问题。例如,我们知道该寄生虫可以被消化吸收,那么它是如何从血流进入眼部的?一旦它进入眼睛,那么它能否在眼部游走?它感染哪种细胞?它是如何被消化吸收的?人体对它们的反映如何?在人类体系中,所有的这些问题至今尚未得到解答。这就是说我们正在做的。我们做出的一些资料可以部分地回答这些问题。因此,近期我们已得出的结论:该寄生虫可能从视网膜血管壁中游离出来以造成感染。因此,眼弓形虫病主要发病部位是视网膜。我们猜想:与眼的其他部位和全身其他部位的血管相比之下,视网膜血管壁本身可能存在某些特殊结构,其可以解释为什么弓形虫易于感染视网膜。因此,当该寄生虫感染人类宿主时,它有使包括视网膜在内的中枢神经系统感染倾向。部分原因可能与一个事实有关--由于免疫赦免,人体没有能力清除该寄生虫;但是,我们认为部分原因可能是,从分子水平上讲,该寄生虫和血管壁间可能存在某种特殊的结构。血管壁从细胞学上说是由内皮细胞组成的,内皮细胞排列于全身血管管壁上。从表面上看,你可能认为,它们是一样的;但是,就你所谈到的组织和动脉血管的种类而言,这些组织的分子组成会有很大的区别。对组织特异性疾病而言,这非常重要。为什么此疾病发生在视网膜而不在肝脏?这些年,我们团队致力于研究:与身体其他部位血管内皮细胞相比,视网膜的内皮细胞是否存在特殊性。我们主要在对比了视网膜内皮细胞和脉络膜内皮细胞。脉络膜是与视网膜毗邻的。因此在研究视网膜血管时,如果你不想把供体牵涉进来,那么脉络膜将是一个最近的位置标记。好的信息是:你可以从人尸上获得眼睛,这样就可以单纯地比较视网膜内皮细胞与该眼睛其他部位内皮细胞间的差异,同时不用考虑不同个体间相应部位差异所带来的干扰。例如 ,如果我们拿你的视网膜内皮细胞和我的脉络膜内皮细胞做实验,那么它们会因为来自于不同个体而不同。如果你想真正地明白视网膜内皮细胞的分子水平特异性,那么就必须对比研究我的视网膜内皮细胞和我的身体(而非你身体的)其它部位内皮细胞;因为如果把你的视网膜内皮细胞和我的脉络膜细胞作对比,它们会不同的。在这种情况下,差异不是存在于脉络膜细胞,而是在于我们俩本就不同这一事实。因此我们团队化大量时间对此进行研究,并且目前已从分子层面上对视网膜内皮细胞有了很好的认识。因此,我们相信视网膜内皮细胞的某方面在该寄生虫感染视网膜过程中起决定作用。我们的研究显示:视网膜内皮细胞含有高水平的黏附因子-- VCAM-1,寄生虫就是依靠此黏附分子进入视网膜的。因此当尝试着建立一个系统来模拟寄生虫从血流进入视网膜的转移过程时,这可以在组织培养体系中完成,和用视网膜内皮细胞来填充此体系然后把它与以脉络膜内皮细胞填充的体系相比时,你在视网膜体系中可以获得大量的VCAM-1,而在脉络膜体系中,你观察不到寄生虫的迁移并且没有发现VCAM-1。我们的研究显示:该寄生虫可能自行地穿过视网膜内皮细胞和该体系的表面可能存在有利于此运动的分子结构。这是为什么该寄生虫会寄宿于视网膜的部分原因。因此,像上面提到过的,世界1/3的人口感染此寄生虫,但是弓形虫的最常见临床表现是视网膜的感染,此被称为眼弓形虫病。这亦是弓形虫病最常见的临床表现。因此,如果从寄生虫学研究团体的角度看待此疾病的话,你会发现此病仅仅好发于免疫力缺陷的人群,如在出生前即已感染的新生儿,或HIV/ AIDS所致的免疫力缺陷的病人。但是实际上,如果你翻阅眼科文献,你就会发现弓形虫患者绝大多数是健康成年人。因此这是一个重要的问题,也是一个世界性的问题。如果你观察的是发展中国家,例如,巴西,眼弓形虫病是儿童致盲的主要病因。令人惊讶的是,很少人致力于该疾病的研究。实际上,我从没有真正地理解它。有一个的寄生虫学团体在致力于此疾病的研究,除此之外,很少人研究此疾病;他们尝试着理解该寄生虫感染人类时的临床基础资料。因此呼吁有一个大的寄生虫学团体,不要求它如研究疟疾的团体一样大。该寄生虫的感染涉及到眼睛和人类眼睛疾病,我们极度缺乏此疾病的研究者群体。



[1]  [2]  [3]  [4]  下一页


 
分享到: 更多
相关搜索
弓形虫病 J.R. Smith  
【本文章已有5 人评论,点击查看。】

用户评论

查看全部评论
推荐视频 more<<  

作者资源

相关标签
2022Euretina  ESCRS 2022  ESCRS 2022  ESCRS 2022  ESCRS 2022  白内障  双周谈  医患  紫外线  叶黄素  膳食补充剂  眼中风  视网膜梗塞  视网膜脱离  干眼  大咖双周谈  双周谈  艾同行 

友情链接

国际循环网

国际糖尿病网

国际肝病网

肿瘤瞭望网

每日医线

国际眼科学和视光学学术会议
设为首页 | 加入收藏 | 关于我们 | 联系方式 | 招贤纳士
声明:国际眼科时讯( www.iophthal.com)对刊载的所有文章、视频、幻灯、音频等资源拥有全部版权。未经本站许可,不得转载。
国际眼科 版权所有 京ICP备18007927号-2   京公网安备 11010502033360号  互联网药品信息服务资格证书编号(京)-非经营性2020-0017
 2011-2022 www.iophthal.com All Rights Reserved