Protective inflammasome activation in AMD

Published on October 31, 2016   44 min
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My name is Matthew Campbell. I'm based at the Smurfit Institute of Genetics in Trinity College Dublin in Ireland. And today, I'm going to talk about some research results that we have that suggest that aspects of the NLRP3 inflammasome may have a protective effect in the degenerative eye disease, age-related macular degeneration, or AMD for short.
AMD is a very prevalent cause of central retinal blindness. And to give you the perspective of AMD in a country the size of Ireland with a population of about 4.5 million, in this country, we have a prevalence of AMD at about 7.2%. So that's roughly aligned with the similar prevalence of AMD that's observed in Western Europe, and in the US where about 10% of individuals over the age of 50 present with AMD of some sort. In Ireland, over 1 million people are over the age of 50 years, and of that, over 70,000 people have some sort of AMD. So this is a very, very common form of blindness. The life expectancy for men in Ireland is approximately 78 years, and for women, it's 82 years. So again, this is very well aligned with figures in Western Europe and even the US. And interestingly, life expectancy has been going up by approximately six hours every day since 1900. And so it stands to reason that with a growing increase in the aging population, the cases of AMD are going to continue to rise, and this is going to present with a very major problem in the years ahead.
So AMD can present in two major forms. One form is called dry AMD, and the other form is called wet AMD. Now, by far, the most common form of AMD is dry AMD. And the classic hallmark pathological feature of dry AMD is the presence of sub retinal deposits in Bruch's membrane called Drusen. Now drusen are extracellular deposits that are processed through the retinal pigment epithelium and they appear as yellowish-white deposits in retinal fundus photos. Now in 10% of cases of dry AMD, it can progress to a form of AMD called wet AMD or neovascular AMD whereby the underlying choroid behind the retina will begin to proliferate into the center of the retina. And these proliferative vessels can actually become very, very permeable, and in some instances, they can actually hemorrhage and bleed, leading to almost instant central retinal blindness. So it's very clear that AMD is a very prominent problem in the aging population and new therapies need to be developed. So in terms of the pathological hallmark of how ophthalmologists determine whether somebody has AMD or not, the classic pathological hallmark featured in retinal photos is the presence of drusen. And what drusen can do, it can distort and damage the retina as it builds up between the choroid and the retina. And when you actually dissect drusen from donor AMD eyes and examine drusen under a microscope, it's particulate, it's oily, it's extracellular in nature. And we asked the question back in 2010 and 2011, well, drusen is extracellular, and it's oily, and it's an extracellular deposit or aggregated material, does it activate the NLRP3 inflammasome.