DONATE MAINS

Neurophysiology and optogenetic applications in the retina

Return

Team leader: Jens Duebel

  • Neuro slide 1

Introduction

We study the structure and function of neural microcircuits in the retina and we develop optogenetic strategies to restore visual function in retinal degeneration.

Presentation


Investigation of neural circuits in the retina:
The retina is a thin sheet of neural tissue in the back of the eye. In the outermost layer of the retina photoreceptor cells convert the incoming light stimuli into electrical signals that are passed via retinal interneurons to ganglion cells that send the information through the optic nerve to higher visual centres. Retinal interneurons are organized in various microcircuits. Each microcircuit extracts visual information such as contrast, colour or the direction of a moving object. However, the functions of most retinal interneurons – in particular retinal amacrine cells – remain unknown. By using two-photon imaging in combination with optogenetic tools and patch-clamp recording, we investigate these microcircuits to uncover their function in visual processing. Finally, this knowledge can help us to develop novel prosthetic devices for the retina.

Optogenetic approaches to restore vision in retinal degeneration:
The insertion of microbial opsins into retinal neurons is a promising approach to restore vision in retinal degenerative diseases, such as Retinitis pigmentosa. Recent studies showed that in these treated retinas light-driven information is transmitted to higher visual centers, and that visually guided behaviours can be mediated through these therapeutic interventions, demonstrating the feasibility of optogenetic approaches to restore light sensitivity in retinal degeneration. However, the light intensity that is needed for optogenetic stimulation is still very high, and current strategies do not allow for discrimination of different wavelengths. Moreover, safety and functionality of microbial opsins have not yet been tested in the primate retina. These experiments are an essential prerequisite for future clinical trials. To overcome these obstacles we will develop optimized optogenetic treatment strategies in mouse models of retinal degeneration by using novel microbial opsins with enhanced light sensitivity and altered action spectra. Through the use of electrophysiology and two-photon imaging we evaluate if sophisticated retinal circuit functions can be restored. Finally, by functional testing of microbial opsins in the primate retina we aim to translate these optogenetic approaches into therapeutic strategies for patients who are affected by retinal degeneration.


Research areas

  • Investigation of neural circuits in the retina by using two-photon imaging in combination with optogenetic tools and electrophysiology.

  • Optogenetic approaches to restore vision: Functional testing of microbial opsins in mouse models of retinal degenerative diseases and pre-clinical validation of optogenetic strategies in non-human primate retinas.


Publications


Support

  • erc
    erc
  • ANR
    ANR
  • Voir et entendre
    Voir et entendre


SUPPORT  Coeur mains