Overview
Age-related macular degeneration (AMD) is a common cause of blindness in older people. We know that genetics and the environment are both involved but we don’t know what triggers the condition.
Lots of research studies have focussed on changes in the light-sensitive layer of the eye (the retina). These studies have shown that a build-up of debris in the retina leads to inflammation. In turn, the inflammation damages cells that are vital for central vision.
But Dr Teeling and team think that long-term (chronic) inflammation throughout the body could also contribute to the damage. So in this project, the team is looking at what role this might play in AMD. They are looking for a ‘signature’ in blood samples from people with long-term inflammatory conditions. They are also testing the effect of system-wide inflammation in an animal model of inflammation in the retina. Results from the study will tell us more about AMD and might also lead to a new approach to treatment by controlling inflammation throughout the body.
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Scientific summary
Age-related macular degeneration (AMD) is a common cause of blindness in the elderly. Both genetic and environmental factors are involved in the pathogenesis but the initiating factors are not known. Many clinical and experimental studies have concentrated on cellular and molecular changes in the retina and these studies have suggested that accumulation of debris-like material, or drusen, between the retinal pigment epithelium (RPE) and Bruch’s membrane, initiates an inflammatory response in the retina causing damage to RPE cells and photoreceptors.
The team hypothesises that chronic systemic inflammation also contributes to pathogenesis via activation of the retinal vasculature and macrophages/microglia. These events may result in increased local inflammation and cellular damage, especially in the presence of retinal pathology. This study aims to investigate the role of systemic inflammation by identifying a systemic immune signature for AMD.
They are utilising a range of immune assays which are validated for detecting innate and adaptive immune activation in blood samples from patients with a chronic inflammatory disease. To dissect the underlying mechanism, the team is using aged mice and their novel mouse model of immune-complex mediated retinal inflammation and testing to find out if systemic inflammation accelerates pathology.
Immune activation is being further studied by blockade of two key pathways of innate and adaptive immunity, using neutralizing antibodies. The study may provide insight into the pathogenesis of AMD but could also lead to novel or optimized therapeutic strategies by modulation of systemic inflammation.