Cata-rotors · Visualising age- and cataract-related changed within cell membranes of human eye lens using molecular rotors
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-11-01 → 2022-01-31
- EU contribution
- €224,934
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
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Results in brief
Visualising age- and cataract-related changed within cell membranes of human eye lens using molecular rotors
The eye lens is considered as one of ideal models of human ageing due to no turnover of its major components, proteins and lipids. Frequently normal age-related changes are followed by the development of opaque and non-transparent regions within the lens, i.e. cataract, which is one of the main reason for the vision loss worldwide. Currently, the surgery is the only way of cataract treatment with significant costs and a heavy burden to National Health Services. Therefore, there is a demand for the understanding of cataract progression at the molecular level, which is currently still unknown. The main goal of this project was to shed the light on age-related changes within plasma membranes of lens cells, which play a crucial role in the transport of nutrients within this avascular tissue. I suggested to use a novel method, Fluorescent Lifetime Imaging Microscopy (FLIM) in combination with fluorescent probes sensitive to polarity and viscosity. The current project was mainly focused on the study of age-related and photo-induced changes in viscosity within plasma membranes of human and porcine eye lenses. Systematic studies of photo-induced damage to plasma membranes have revealed different changes in viscosity depending on the reaction mechanisms (electron transfer or singlet oxygen). The work with non-fixed human lens has shown that morphology of cells is significantly affected by the tissue fixation and demonstrated the presence of cells with three different structures and dynamic properties of plasma membranes within a non-fixed tissue. The results illustrate that FLIM method is highly promising to study ocular tissues, providing new data about fundamental processes about normal ageing and disease progression.
Data: CORDIS, © European Union
Project 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.
Original text from CORDIS.
Participants
- IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE · LondonCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union