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Retina Epithelium Mechanobiology and Diseases

Jacopo Di Russo

Epithelia are sheets of cells self-organized either as a simple single-cell monolayer or as complex 3D structures. Their structures and functions are not defined by biochemical processes alone, but they are also highly dependent on their physical characteristics. These have been shown to be emerging properties of cell collectives, not predictable from single cell biomechanics.

 

The extracellular matrix (ECM) underlying epithelia is a pivotal player in both signaling of biochemical information to the cells and in controlling mechanical properties. Our research aims to understand this interplay in the development and function of the retinal pigment epithelium (RPE), which is critical for the support of the neuroepithelial cells and responsible for light detection/sight. As in all epithelia, RPE cells tightly adhere to the underlying basement membrane (BM), which is the proximal part of the thicker ECM layer called Bruchs membrane (BrM). While the BM components carry the biochemical information for RPE adhesion, deeper layers of the BrM, composed of fibrillar collagen types I, III and V and elastin fibers, are proposed to determine physical properties of RPE.

 

Our interdisciplinary experimental approaches combine hydrogel technologies with retina organoids and mouse biology to understand the contribution of the BrM molecular and structural components to the mechanobiology of RPE and its functional interaction with the retinal neuroepithelium.

 

The investigation of these unexplored aspects of RPE physiology aims to provide new insights into the understanding of severe retina diseases such as Age-related Macular Degeneration and to develop innovative therapeutical approaches.