Extracellular matrix in the healthy cornea
A major focus in our laboratory is understanding cell-ECM interactions and their impact on the structure and functions of the cornea. The transparent cornea provides two thirds of the refractive power of the eye and serves as a protective barrier through unique adaptations of the cells and the ECM. The stromal ECM connective tissue is a highly organized array of collagen fibrils and regulatory proteoglycans produced by a specialized type of fibroblast, the keratocytes (Scott, 2011). We are investigating properties of keratocytes, their development and whether these cells can be maintained in culture to produce a cornea-like stromal ECM (Foster, 2018). The stromal ECM has precisely stacked, uniformly thin collagen fibrils that gives the cornea its transparent and refractive qualities for optimal vision. We discovered that lumican is a key proteoglycan that helps to assemble uniform collagen fibrils, and gene-targeted lumican-null mice have thick, laterally fused collagen fibrils and develop corneal opacity (Chakravarti, 1998; Chakravarti, 2006).
We are developing cornea organoids using induced pluripotent stem cells to explore cell-ECM interactions in a 3D cell culture model system (Foster, 2017). These organoids mimic certain features of the cornea and therefore, may be used to understand early events in the development of the cornea. The organoids are also being used in functional analyses of genes active in the cornea.