Inflammasome IL-18 Controls AMD Development
Author: Trinity College Dublin
Published: 2012/04/16 - Updated: 2026/01/25
Publication Type: Research, Study, Analysis
Category Topic: Blindness - Vision Loss - Related Publications
Contents: Synopsis - Introduction - Main - Insights, Updates
Synopsis: This research from Trinity College Dublin's Ocular Genetics Unit identifies a critical mechanism in age-related macular degeneration (AMD), the leading cause of vision loss in adults over 50. Scientists discovered that drusen deposits in the macula trigger inflammatory components, particularly IL-18, which acts as a protective anti-angiogenic factor. The findings, published in Nature Medicine and supported by major health foundations, suggest that controlling IL-18 levels could prevent progression from dry AMD to the more severe wet form - potentially revolutionizing treatment for millions of older adults who currently face central vision loss that impacts reading, driving, and daily independence - Disabled World (DW).
Introduction
Scientists at Trinity College Dublin have discovered that a part of the immune system called the inflammasome is involved in regulating the development of one of the most common forms of blindness, called Age-Related Macular Degeneration (AMD). They have discovered that controlling an inflammatory component IL-18, in cases of Age-Related Macular Degeneration (AMD) could prevent the development of the disease.
Main Content
Age-Related Macular Degeneration (AMD) is a common eye condition among people age 50 and older. It is a leading cause of vision loss in older adults. It gradually destroys the macula, the part of the eye that provides sharp, central vision needed for seeing objects clearly. In some people, AMD advances so slowly that vision loss does not occur for a long time. In others, the disorder progresses faster and may lead to a loss of vision in one or both eyes. The vision loss makes it difficult to recognize faces, drive a car, read, print, or do close work, such as sewing or fixing things around the house.
The disease AMD involves loss of central vision, people with advanced disease being unable to read, watch TV, enjoy the cinema, drive, or use a computer - in short, everyday living becomes very difficult. The research, which is published this week in the international medical journal, Nature Medicine, is supported by Science Foundation Ireland, the American Health Assistance Foundation (AHAF), the Health Research Board (HRB) and Fighting Blindness Ireland.
The key diagnostic feature of AMD is the presence of "drusen", which are recognized during an eye exam as yellowish/white deposits in the central region of the retina called the macula.
Dry AMD is characterized by the presence of excessive amounts of drusen and there are currently no forms of therapy other than recommended lifestyle changes such as giving up smoking, which is a recognized risk factor. However, a significant number of cases of the "dry" form of AMD can progress to the "wet" form, where blood vessels underneath the retina begin to grow, leading to central blindness. If you hold two coins immediately in front of your eyes, you will see a single large black circle blocking out your central vision. This is a very realistic simulation of what it is like to live with advanced disease.
The leading co-authors of the Nature Medicine paper, Trinity College scientists, Dr Sarah Doyle and Dr Matthew Campbell have together discovered that drusen accumulating in the macula can lead to the production of two inflammatory components termed IL-1beta and IL-18. These findings were based on studies involving drusen isolated from donor AMD eyes in tandem with pre-clinical studies on models of the disease.
"Traditionally, inflammation in the retina or indeed the eye in general is not beneficial and is a pathological hallmark of many eye diseases, including AMD. However we have identified, that one inflammatory component termed IL-18 acts as a so-called anti-angiogenic factor, preventing the progression of wet AMD" says Dr. Campbell.
"The progression from "dry" to "wet" AMD appears to be mediated by the inflammatory component IL-18, our results directly suggest that controlling or indeed augmenting the levels of IL-18 in the retinas of patients with dry AMD could prevent the development of the wet form of disease, which leads us to an exciting new prospect for a novel therapy for AMD" says Dr Doyle.
The research was undertaken at Trinity College's Ocular Genetics Unit, Director, Professor Pete Humphries and at the laboratories of Professor Luke O'Neill at the Trinity Biomedical Sciences Institute, in collaboration with Professor Joe Holyfield at the Cole Eye Institute at Cleveland, Ohio.
Full Title of the Paper:
NLRP3 has a protective role in age-related macular degeneration through the induction of IL-18 by drusen components
Insights, Analysis, and Developments
Editorial Note: What makes this 2012 breakthrough particularly significant is its shift in how researchers view inflammation in eye disease - previously considered purely harmful, IL-18 was found to actually protect against the wet form of AMD progression. This paradox opens doors for targeted biological therapies that work with rather than simply against the immune system. For individuals diagnosed with dry AMD, this research validates hope for intervention strategies that could preserve central vision before irreversible damage occurs, while also demonstrating how understanding the complex biology of common conditions affecting seniors and people with disabilities leads to treatments that improve quality of life and independence - Disabled World (DW).Attribution/Source(s): This quality-reviewed publication was selected for publishing by the editors of Disabled World (DW) due to its relevance to the disability community. Originally authored by Trinity College Dublin and published on 2012/04/16, this content may have been edited for style, clarity, or brevity.