Abstract
Purpose :
Mechanical signals such as the pressure play a key role for retina shape development and the maintenance of a healthy phenotype. Consequently, mechanical abnormalities have been identified as risk factors for retina diseases including myopia and glaucoma.
A global mechanical signal might translate into changes in the mechanics of the cellular microenvironment to ultimately affect cell behavior. However, this mechanical cascade is not understood due to a lack of techniques to measure tissue mechanical properties inside the retina.
Our aim is to quantify (I) the effect of the global pressure to changes in the mechanics of the cellular microenvironment and (II) their influence on cell viability.
Methods :
We measure the mechanical properties of retina organoids which we derive from mouse embryonic stem cells according to published protocols (Völkner et al., Stem Cell Reports, 2017).
Applying a technique recently developed by us (Serwane et al., Nature Methods, 2017; Mongera et al., Nature, 2018) we insert cell-scale ferrofluid droplets in different retina locations and apply a controlled magnetic field to induce their deformation. Recording the dynamical tissue response, we locally determine the full viscoelastic properties, as a function of retina layer. To study how a global increase in pressure affects the mechanics of the cellular microenvironment and cell viability, the osmotic pressure is controlled using Mannitol and cell viability is assessed via fluorescence imaging.
Results :
We find that the retina organoid is a viscoelastic material, elastic on a second timescale and fluid on the timescale of one minute. Furthermore, we reveal the existence of a yield stress, the amount of stress necessary to induce plastic deformations which can lead to irreversible morphological tissue changes in the retina organoid.
Conclusions :
The magnitude of the yield stress controls the retina’s mechanical integrity and thus its susceptibility to deformations. Moreover, a variety of cell behavior, including cell viability, is affected by mechanical signals from the cellular microenvironment. Therefore, the quantification of mechanical signals is an essential step towards a mechanistic understanding of mechanically related retina diseases.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.