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]PEDF作用机制研究
——美国南卡罗莱纳医科大学Craig E. Crosson教授专访

眼科基础研究  作者:  C.E.Crosson  2013/7/9 16:29:00
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:Crosson医生,非常感谢您的参与。您在关于色素上皮衍生因子PEDF的研究方面已经做了很多工作。您认为其肽段的具体作用机制是怎样的?

  <International Ophthalmology Times>:Dr. Crosson, thanks for joining us. You have done a lot of work in the PEDF Study. What is the specific mechanism of that peptide?

  国际眼科时讯:Crosson医生,非常感谢您的参与。您在关于色素上皮衍生因子PEDF的研究方面已经做了很多工作。您认为其肽段的具体作用机制是怎样的?

  Dr. Crosson:Very good question, we are still trying to understand how it operates. Even with this specific peptide, identifying the exact receptor that it interacts with or protein that it binds to cause these effects is still not well resolved. There have been suggestions but no clear answers. We have looked at how the two interact to regulate the blood-ocular barriers. While VEGF basically reduces the barrier function and in that sense allows more things to come in, PEDF opposes that, and our studies are really designed to look at that mechanism, how do they oppose it.

  VEGF does a number of things. It is also angiogenic but the part of VEGF that we are actively pursuing at the moment is not its basal proliferative activity but its ability to change the blood-ocular barrier, specifically in diabetes and its relationship then to macular edema. We know that some of the diabetic macular edema trials that you can use the anti-VEGF compounds such as Lucentis to treat these, but there are endogenous anti-VEGF compounds, one of them being PEDF that appear to oppose its action. If we could understand these endogenous mechanisms, perhaps we will understand the pathophysiology better but we will have new opportunities for developing drug to treat diseases such as diabetic retinopathy.

  Crosson医生:好的,我们一直在研究它是如何作用的。即使是这个特定的肽段,确定它确切相互作用的 受体或是与其结合起作用的蛋白质尚未明确。现在仅是有某种可能及建议,还没有明确的答案。我们已经看到了两者相互作用调节血眼屏障。而VEGF基本上降低屏障功能,在这个意义上允许更多的物质进入屏障内,PEDF与其相反,我们的研究的目的就是明确其作用机制,观察其如何起到相反的作用。

  VEGF有一系列的用途,它可以促血管生成。但是我们此时想知道的不是其基本的增殖活性,而是其改变血眼屏障的能力,尤其是在糖尿病和与其相关的黄斑水肿。我们知道,一些糖尿病黄斑水肿临床试验中,可以使用抗VEGF化合物如雷珠单抗注射液治疗这些疾病,但也有内源性抗VEGF化合物,其中之一就是PEDF,表现为相反的作用。如果我们能够理解这些内源性抗VEGF化合物的作用机制,可能我们就能更好地理解这些病理机制,我们就有新的机会去发展药物来治疗疾病,如糖尿病视网膜病变。

  <International Ophthalmology Times>:What caused you to become so tremendously interested in the PEDF peptide?

  国际眼科时讯:是什么让您对PEDF感兴趣的?

  Dr. Crosson:Basically like with most studies, it comes out of a young person wanting to do an experiment that found a very interesting response that was unexpected and opened up a whole new series, a whole new line of studies for us. The great thing about having students, young investigators in your lab is their imagination and their creativity. And this is an example of how an entire project get started out of just one person asking an imaginative question.

  Crosson医生:就像大多数研究一样,它源于一个年轻人想做一个试验,结果发现了一个有趣的现象,这个反映超出预期并开启了一个新的研究系列,指明了新的研究方向。做科研最重要的事情,就是在你实验室中的学生、调查员要有想象力和创造力。曾有一个例子表明一项研究项目的开展,就起自一个人问了一个非常有创造力的问题。

  <International Ophthalmology Times>:Great. It’s extremely difficult to treat ischemia-induced retinal degeneration, and your study show that the ASM inhibitor could help in retinal ischemic disorders. Can you tell us where you are in the study of ASM and what is the next step?

  国际眼科时讯:非常好。缺血诱导的视网膜变性难以治疗,你的研究表明,ASM抑制剂可以在视网膜缺血性疾病治疗起到一定作用。您能谈一下您在ASM研究中的工作定位和下一步的工作内容吗?

  Dr. Crosson:Basically this is a study looking at how lipid metabolites influence retinal function in response to stress. And so this is another example of a young investigator asking a new question, to ask what is the cascade of events that lead to retinal degeneration in ischemia or in glaucoma and trying to just sort out all of them. There are multiple factors but we are trying to understand what are the very early changes.

  This appears to be a very early change is that the metabolism of some very specific lipids by an enzyme called acid sphingomyelinase . And the products that they produce and how those products then influence retinal function and retinal degeneration is also in a very early stage. While the data is interesting and suggested that these pathways are important, we still have a long way to go.

  Crosson医生:这个研究是为了观察脂质代谢产物在如何影响视网膜功能以应对压力。这是另外一个年轻的试验者提出的新问题,来思考在缺血和青光眼中导致视网膜变性的一系列事件是什么,如何解决。其中有非常多的影响因素,但是我们正在寻找最早期的改变。

  一个非常早期的改变是,由酸性鞘磷脂酶介导的一些非常特殊的脂类代谢。他们的代谢产物的产生,以及这些代谢产物影响视网膜功能和视网膜变性也是在非常早期的阶段。尽管这些数据非常有趣,而且提示这些路径非常重要,我们仍有很长的路要走。

  <International Ophthalmology Times>:I am impressed that you have talked a lot about how the young investigators are the ones that are bringing up these new topics in your lab. Being the overseer of that lab, what is your technique to encourage them to be creative and to make these new discoveries?

  国际眼科时讯:我印象中你已经谈了很多关于年轻研究人员提出新课题的内容,作为实验室的主管,您如何鼓励他们去创新,并提出这些新发现?

  Dr. Crosson:The key is encouraging them to first get a good foundation of knowledge, to read, to understand not just what’s going on in the eye but have a good understanding of physiology in general, biochemistry, and then begin to just pose some questions to them and let them think about, what do they think is going on and giving them the opportunity to try new experiments.

  The problem right now is that not only in the U.S. but around the world as the economy is shrinking, we are truly in danger of losing a whole generation of scientists and while that may not impact us in the next 6 months, 6 years, 10 years, 15 years from now, I think our ability to find new curers could be substantially reduced if we don’t find a way to encourage new scientist to take this up.

  Crosson医生: 首先最关键的是鼓励他们有一个非常好的知识基础,去阅读,去理解知识,而且不仅要掌握眼球的相关知识,同样要对基本的生理、生化知识有很好的理解,然后开始提出一些问题让他们去思考,并加以理解,并给予他们机会去尝试新的试验。

  现在的问题是,不仅是在美国,全世界经济萧条,我们面临着失去一整代科学家的危险,也许这并不影响在接下来6个月,6年,10年甚至15年以后的工作,但是如果我们没有能够找到一个办法鼓励新的科学家成长的话,我想我们将来发现新的医疗者的能力将会大大下降。

  <International Ophthalmology Times>:Dr. Crosson, I understand you are working on models to investigate RPE function in vivo. Can you tell me a little more about that?

  国际眼科时讯:Crosson医生,我知道您正在探索研究体内RPE功能的模型,能谈一下相关内容吗?

  Dr. Crosson:Over the last several years, there has been tremendous strides made in understanding the retinal pigment epithelium and as well as the outer blood-retinal barrier but also its ability to support the neural retina, specifically the photoreceptors in a variety of ways. However, most of these have really been in vivo assays. We developed a number of transgenic mice that have allowed us to work at this in vivo but there are several functional…it’s very difficult to look at this in terms of its function independent of other vascular systems and so what we wanted to do to look at different species because there are some that don’t have any inner retinal circulation. It all comes from the choroidal circulation and, therefore, the barrier is primarily formed, the blood-ocular barrier is primarily formed by the retinal pigment epithelium.

  In those cases, understanding how edema forms and fluid is removed from that is much easier in those animal models. And this was an attempt to do this and the species we chose was a rabbit because it has a relatively avascular inner retina. And we can then look at the RPE function independent of that. We are really the first ones to use OCT high-resolution imaging to look at this and come up with some very quantitative estimates of how the RPE functions in vivo

  Crosson医生:在过去的几年中,在视网膜色素上皮、外血-视网膜屏障和其支持神经视网膜(特别是在各种形式的感光细胞)的能力方面的理解已经有了巨大的进步。然而,大部分是通过活体测定的。我们利用一些转基因小鼠,以便我们完成体内功能研究,但是体内有许多功能,我们很难独立于其他循环系统对其进行功能研究,因此,我们想观察不同物种,因为其中有一些不存在视网膜内循环。这一切都来自于脉络膜恶性循环,因此,屏障是最先形成的,血眼屏障主要由视网膜色素上皮细胞组成。

  在一些案例中,在动物模型中理解水肿形成和液体消失更容易一些。我们试图做到这些,选择的物种是家兔,因为家兔有一个相对无血管的内层视网膜。我们可以独立观察RPE的功能。我们先驱性地使用OCT高分辨成像来观察RPE,并提出体内RPE功能的定量估算。

 


 
分享到: 更多
相关搜索
C.E. Crosson 色素上皮衍生因子 视网膜色素上皮 
【本文章已有1 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