Modulation of corneal tissue mechanics influences epithelial cell phenotype

Abstract

Whilst the control of stem cell differentiation using substrates of differing compliance has been extensively explored in vitro, the significance of this mechanism at a physiological level is not known. Here we set to explore the role of corneal surface biomechanics in controlling epithelial cell proliferation and differentiation. Using non-contact high-resolution Brillouin spectro-microscopy we showed that the corneal outer edge (limbus) has significantly lower bulk modulus compared to the central cornea, and that this difference is precisely delimited in the organ. Furthermore, the areas of the limbus with distinctly softer properties were shown to be associated with limbal epithelial stem cell (LESC) residence. Based on these findings, we then provided the first demonstration of the capacity to modulate LESC phenotype, both in vivo and ex vivo, solely through the recreation/restoration of suitable biomechanical niches. These results thus confirm the fundamental role of corneal biomechanics in directing epithelial stem cell behavior.