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Role of miRNAs in the retinal bipolar cell post-synaptic response

English title Role of miRNAs in the retinal bipolar cell post-synaptic response
Applicant Cronin Therese
Number 139705
Funding scheme Marie Heim-Voegtlin grants
Research institution Friedrich Miescher Institute for Biomedical Research
Institution of higher education Institute Friedrich Miescher - FMI
Main discipline Molecular Biology
Start/End 01.02.2012 - 31.01.2013
Approved amount 115'172.00
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Keywords (3)

synaptic transmission; Retinal bipolar cells; MicroRNAs

Lay Summary (English)

Lead
Lay summary

It is in the retina, a light-sensitive tissue at the back of the eye that the first steps of vision occur. Millions of retinal neurons are involved in the complex pattern of communication that allows the tissue to detect and process light and to transmit the information to the brain’s visual cortex. One of the many important functions of the retina is to carry out light-dark adaptation, a process which requires tight regulation of retinal neuronal function. Much is known about the cells that control such adaptation, with the retinal bipolar cells being the key-players in the processing of the light signal. However there remain gaps in our understanding of the mechanisms that allow the cells to make short-term and rapid responses to changes in light intensity. This is especially true at the level of gene regulation in the bipolar cells. An important mechanism the cell has in controlling protein activity is to simply reduce the quantity of protein being made. Proteins are derived from the translation of messenger RNAs, the molecules that make up the chemical blueprint of a cell. By interrupting RNA translation, the cell can put a transient block on protein expression allowing the cell to meet continually changing demands for protein production. This method of regulation is ideal for the rapid changes in neuronal activity that govern many visual responses. MicroRNAs are a special class of RNA devoted to exactly this type of regulation. Recent evidence has shed light on the distinctly important role that microRNAs play in neurons and in retinal neurons in particular. By investigating the microRNAs of the retinal bipolar cells we may come to a deeper understanding of the signal processing power of the retina. Importantly, this may enable us to further our understanding of the diseases that can interfere with the retina’s function and lead to blindness. In the context of the retina as a part of the central nervous system this may in turn strengthen our understanding of the mechanisms of neuronal processing and neurodegeneration as a whole.

Direct link to Lay Summary Last update: 21.02.2013

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Abstract

MicroRNAs are non-protein-coding RNA molecules which have an inhibitory effect on protein expression. Links have been established between aberrant miRNA expression and neuronal disorders. Many miRNAs are enriched in the photosensitive neural tissue of the eye called the retina. The cone photoreceptors cells mediate day-time vision and are the first target for investigation when studying visual function. Recent work from the FMI in Basel shows severe consequences of blocking miRNA activity in mouse cone photoreceptors. Loss of cone-specific miRNAs results in complete loss of all cone-specific gene expression rendering the cell non-functional. I propose to investigate the effects of miRNA function downstream of the cone cell - in the retinal bipolar cells where the initial steps of visual processing occurs. In addition to yielding expected insights into visual processing, the focus on the bipolar cells will allow us to investigate the role of miRNAs on neurotransmission at highly active synaptic sites.
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