Retina Organoid Neuronal Network

Friedhelm Serwane, Projektleiter

Fluorescence image of retina organoid. The retina organoid develops a typical tissue morphology (left: day 8 organoid; cyan actin-gap) and cell types which are organised into distinct layers (right: day 24 organoid; cyan rx-gfp, yellow DAPI, magenta pax6-AF594) — Fluorescence image of retina organoid. The retina organoid develops a typical tissue morphology (left: day 8 organoid; cyan *actin-gap)* and cell types which are organised into distinct layers (right: day 24 organoid; cyan rx-gfp, yellow *DAPI,* magenta pax6-AF594)

Friedhelm Serwane

Fluorescence image of retina organoid. The retina organoid develops a typical tissue morphology (left: day 8 organoid; cyan *actin-gap)* and cell types which are organised into distinct layers (right: day 24 organoid; cyan rx-gfp, yellow *DAPI,* magenta pax6-AF594)

Friedhelm Serwane

Part of our team moved to LMU Munich. Please visit us here:

Our group is particularly interested in revealing the mechanical aspects in the processing of neuronal signals. To illuminate the role of mechanics, we will use ferrofluid droplets as mechanical actuators, a technique which has been developed by us (Serwane et al., Nature Methods, 2017 https://www.nature.com/articles/nmeth.4101) and is now used to understand the role of mechanics in 3D developing tissues (Mongera et al., Nature 2018, in press https://www.nature.com/articles/s41586-018-0479-2).

The project integrates concepts of physics and biology to develop an organotypic model system for the human eye based on retina organoids. The high accessibility and tunability of our in vitro system will allow us to address three fundamental questions at the interface between physics and biology:

What are the mechanical and chemical cues that orchestrate the self-organization of retina tissues?
How are light-induced neuronal signals processed within these tissues?
Can we bio-engineer artificial tissues with similar functionalities?

A retina organoid which we derive from mouse embryonic stem cells serves as a building block for our in vitro model (left; day 8 organoid; cyan actin-gfp; right: day 24 organoid; cyan rx-gfp, yellow DAPI, magenta pax6-AF594). Spatiotemporal patterns of light will be used to stimulate neuronal activity within the retina tissue which we will then quantify using neuroscience tools such as calcium imaging and optogenetics.

(A): 3D lightsheet microscopy of firing neurons (organoids grown in our laboratory). A calcium sensor (gCamp6s) is used to measure neuronal activity. (B) Neuronal activity within a single plane. (C) Calcium wave propagating across three neurons.

(A): 3D lightsheet microscopy of firing neurons (organoids grown in our laboratory). A calcium sensor (gCamp6s) is used to measure neuronal activity. (B) Neuronal activity within a single plane. (C) Calcium wave propagating across three neurons.

Correlating local mechanical properties with neuronal network function will allow us to understand how mechanical stimuli can trigger and influence neuronal responses.

Beyond basic research the system we prepare will open the door to personalized mechanical diagnosis of retina diseases. Mechanical abnormalities are key risk factors for pathological conditions. Therefore, finding new diagnosis and treatment tools targeting tissue mechanics might pave the way to novel approaches tackling retina diseases.

Patents:

EP3332695A1; Friedhelm Serwane, Joachim Spatz: Einstellbares neuronales Netzwerk und künstliches Auge