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Visualising age- and cataract-related changed within cell membranes of human eye lens using molecular rotors

Project description

Insight into the cataract-associated structural changes of the lens

Intriguingly, there is no turnover in lipids and proteins in the lens of the mammalian eye. As a result, defects in these molecules during ageing alter membrane structure and impair metabolite transport, causing cataract, a condition associated with clouding of the lens. The EU-funded Cata-rotors project will use fluorescence lifetime imaging microscopy to determine age-related changes in the structure of lens cell membranes and how they lead to cataract development. Oxidation-induced damage in an animal model will also shed light on the general mechanism of lens ageing, paving the way for novel treatments for cataract.

Objective

The lens of a mammalian eye is a unique tissue, which maintains high transparency during an individual lifespan, yet has no protein and lipid turnover. Thus, the eye lens is considered as one of ideal models of human aging. With age the proteins and lipids of the lens accumulate numerous post-translational modifications, leading to defects in the cell membrane structure and, therefore, to impairments of metabolite transport. The retarding of the metabolite exchange predisposes the lens nucleus to oxidative stress – a key factor in the formation of cataracts. Therefore, a study of the normal functioning of the lens, as well as age- and cataract-related changes in metabolite transport through the lens cells may shed light on the general mechanism of the lens aging and cataractogenesis. The present project is aimed at investigating and directly quantifying age- and cataract-related changes in the properties of cell membranes of the human eye lens by Fluorescence Lifetime Imaging Microscopy (FLIM), employing fluorescent viscosity-sensitive probes termed ‘molecular rotors’. We envisage that the results obtained will show the distribution of viscosity within membranes of fibre cells and will allow to directly visualise how the age and the early stages of cataract influence on fluidity of these lipid bilayers, which are of vital importance in maintaining the clarity of our eye lens and our vision. Analysis of age-related changes in the structure of membrane proteins and experiments with animal eye lenses subjected to photo-oxidation and chemical oxidation will provide additional information on the mechanisms of age- and cataract-related changes in viscosity within lens fibre cell membranes. Overall, this project addresses issues of fundamental importance in biophysics, as well as provides underpinning knowledge for understanding of health and disease and the treatment of an important eye condition: cataract.

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Coordinator

IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Net EU contribution
€ 224 933,76
Address
South kensington campus exhibition road
SW7 2AZ London
United Kingdom

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Region
London Inner London — West Westminster
Activity type
Higher or Secondary Education Establishments
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Other funding
€ 0,00