RETICIRC

Circuit specific approaches to retinal diseases

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 Obiettivo del progetto (Objective)

'The RETICIR project focuses on neuronal mechanisms of vision from photoreceptor level to visual cortex. Physiological knowledge of the visual system will be used to address pathophysiological neuronal mechanisms of diseases affecting vision. In the project we will identify molecular and cellular disease mechanism of retinitis pigmentosa and glaucoma, and will demonstrate restoration of vision in retinas with degenerated photoreceptors from single neuronal responses in the retina all the way to cortical visual evoked responses and behavioral assays.Blindness in man often results from dysfunction of the retina. For a number of retinal diseases, the retinal circuitry is a major part of the problem. Effective strategies for treatment of those diseases and for all attempts to restore vision, understanding of the retinal circuitries is essential. Our strategy is that understanding the structure and function of specific retinal circuits should be used to find therapies to retinal diseases, like for instance retinitis pigmentosa and glaucoma. Specific circuits can be only studied with cell type specific promoters and therefore the methodology that we will use is the combination of in vivo marked cell types with genetic interference with the function of these cells and state of the art physiological and behavioral approaches.'

Introduzione (Teaser)

Retinal dysfunction most often leads to human blindness. Any attempt to counter this calls for a better understanding of the neuronal mechanisms of diseases affecting vision.

Descrizione progetto (Article)

Some retinal diseases lead to photoreceptor degeneration, while the rest of the retina is initially left intact. This suggests that retinal circuitry plays a major role in the development of retinal diseases when leaving important areas exposed to harmful 'environmental' effects.

The 'Circuit specific approaches to retinal diseases' (Reticirc) project is eager to show that if the degenerated photoreceptors or neurons in the outer retina can be artificially stimulated, a certain degree of vision can be restored. Enhanced knowledge of the structure and function of specific retinal circuits can be used to discover therapies for retinal diseases such as retinitis pigmentosa and glaucoma.

In general, work is focusing on examining basic retinal signal processing. The aim is to test how photoreceptor degeneration takes place in retinitis pigmentosa by testing the bystander hypothesis. This hypothesis, or effect, puts forward the theory that the more 'onlookers' there are, the less likely any of them will come forward to help in a situation of emergency.

This is relative here considering that cone cells are more resilient to light insult than rods are, but less in volume. However, the loss of rods in the retina is more severe as this may leave cone cells exposed.

Another focus is to develop optogenetic techniques to restore light sensitivity in degenerated photoreceptors and second-order neurons (nerve cells) in the retina.

Significant progress has been made in efforts to describe the outer retina, while a quantitative model of photoreceptors has been developed and validated. The functional properties of specific ganglion cell classes have also been described.

Reticirc researchers have managed to provide a quantitative functional description of the feedback pathway from horizontal cells to cones, and demonstrated that negative feedback along this pathway is done without the mediation of a neurotransmitter.

The researchers have been successful in restoring sensitivity to light in degenerated photoreceptors of mice as well as applying the technique on human retinal explants. Project accomplishments so far affirm the Reticirc consortium's conviction that the optogenetic strategy represents a viable means of restoring vision.