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

Descrizione del progetto

Approfondimento sui cambiamenti strutturali del cristallino associati alla cataratta

Curiosamente, nel cristallino dell’occhio dei mammiferi non vi è alcun ricambio di lipidi e proteine. Di conseguenza, i difetti di queste molecole durante l’invecchiamento alterano la struttura della membrana e compromettono il trasporto dei metaboliti, causando la cataratta, una condizione associata all’annebbiamento del cristallino. Il progetto Cata-rotors, finanziato dall’UE, sfrutterà la microscopia di imaging a fluorescenza a vita per determinare i cambiamenti legati all’età nella struttura delle membrane delle cellule del cristallino e il modo in cui questi portano allo sviluppo della cataratta. Il danno indotto dall’ossidazione in un modello animale farà anche luce sul meccanismo generale dell’invecchiamento del cristallino, aprendo la strada a nuovi trattamenti per la cataratta.

Obiettivo

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.

Campo scientifico (EuroSciVoc)

CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP.

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Meccanismo di finanziamento

MSCA-IF-EF-ST - Standard EF

Coordinatore

IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Contribution nette de l'UE
€ 224 933,76
Indirizzo
SOUTH KENSINGTON CAMPUS EXHIBITION ROAD
SW7 2AZ LONDON
Regno Unito

Mostra sulla mappa

Regione
London Inner London — West Westminster
Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
€ 224 933,76