H2020Individual fellowship2017–2019

ZINCLAPS · Light-addressable potentiometric sensors (LAPS) for zinc imaging with high spatiotemporal resolution for elucidating the role of zinc in age related macular degeneration.

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2017-06-21 → 2019-08-24
EU contribution
€195,455
Participants
1
Scheme
MSCA-IF-EF-ST

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Results in brief

Light-addressable potentiometric sensors (LAPS) for zinc imaging with high spatiotemporalresolution for elucidating the role of zinc in age related macular degeneration.

Light-addressable potentiometric sensors (LAPS) have great potential as a tool for functional electrochemical imaging of the attachment area of cells, providing information such as ion concentration, extracellular potentials and ion channel activity. The technique is particularly attractive for analysing cell responses of cells with planar polarisation as the cell-surface attachment area is not accessible to conventional electrophysiological measurements. The technique has the advantage that different spots on a flat, featureless electrolyte/insulator/silicon field effect structure can be addressed by scanning a focused light beam across the sample thereby exciting local photocurrents and generate an electrochemical image. However, current systems suffer either from poor resolution or slow scanning speed to monitor biological processes. In this project, we aimed to develop an electrochemical scanning setup with high spatiotemporal resolution that allows imaging of physiological processes with subcellular resolution and in real time. The setup can be used with different ion sensitive surfaces to monitor the extracellular ionic flux and its role in cellular processes. The new instrument will lend itself to the investigation of disease mechanisms, the effects of toxicity and efficacy of drugs. In the long term, this could aid the development of organ on-a-chip devices, which can reduce the need for animal models. More specifically, we are planning to develop a zinc sensitive surfaces and use them in conjunction with the high-resolution and high-speed imaging setup to investigate the role of zinc in age related macular degeneration (AMD), the mechanism of which is still not well understood. This may lead to new treatments to prevent, forestall, or reverse the effects of the disease and elucidate zinc's role in other diseases including type 2 diabetes, pancreatic cancer, and Alzheimer disease and is therefore expected to impact the pharmaceutical industry and increase the quality of life for an ageing population. The main objective of this project was to develop a high-speed and high-resolution LAPS setup with the capability of visualizing dynamic physiological events in a microenvironment. In particular, we were interested in real-time imaging of physiological parameters of living cells and establish protocols for studying their interactions with drugs and toxins.

Data: CORDIS, © European Union

Project objective

Light-addressable potentiometric sensors (LAPS) have great potential as a tool for functional electrochemical imaging of the attachment area of cells, providing information such as ion concentration, extracellular potentials and ion channel activity. The technique is particularly attractive for analysing cell responses of cells with planar polarisation as the cell-surface attachment area is not accessible to conventional electrophysiological measurements. However, current systems suffer either from poor resolution or slow scanning speed. In this project, we propose to develop a novel LAPS setup with high spatiotemporal resolution combined with two-photon fluorescence microscopy that allows imaging of physiological processes with submicron resolution and in real time. Novel zinc sensitive surfaces will be developed and used in conjunction with the new high-resolution and high-speed LAPS setup to investigate the role of zinc in age related macular degeneration (AMD). The retina and the underlying retinal pigment epithelium contain high concentrations of zinc. Several eye disorders are associated with altered zinc balance, and zinc supplementation has become a choice of treatment for diseases like agerelated macular degeneration. Despite its importance in health and diseases of the eye, it is still not well understood how zinc participates in cellular and molecular events and how zinc supplementation might be beneficial. We will investigate zinc fluxes at the basal side of the retinal pigment epithelium where zinc is suspected to play a key role in the formation of deposits and the initiation of AMD. The results of the study may lead to new treatments to prevent, forestall, or reverse the effects of the disease and may also help to elucidate zinc's role in other diseases including type 2 diabetes, pancreatic cancer, and Alzheimer disease and are therefore expected to impact the pharmaceutical industry and increase the quality of life for an ageing population.

Original text from CORDIS.

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Data: CORDIS, © European Union