Cell Adhesive Interactions in Ocular Health and Diseases

The role of cell adhesive interactions (both cell-matrix and cell-cell) in regulation of various cellular processes and diseases is well-recognized. Cell-matrix interactions, which are involved in connecting the intracellular cytoskeleton to the extracellular matrix through transmembrane proteins and integrins, have been extensively studied in various cell types. Cell-matrix adhesions including focal adhesions (FAs) and podosomes, are large and dynamic multicomponent complexes comprised of many scaffolding and signaling proteins. FAs are robust and stable ECM contacts, associated with contractile actin stress fibers, while podosomes are adhesion complexes that degrade the underlying matrix and promote cell migration. Focal adhesion proteins also interact with various cell-cell junctional complexes, and the components of both these adhesive complexes interact with the cytoskeletal network. The translation of physical forces derived from stretching, ECM rigidity, and compression into biochemical signaling pathways is known as mechanotransduction, and FAs, cell-cell adhesion complexes, and stretch sensitive membrane channel proteins play a crucial role in mechanotransduction. A growing body of evidence suggests that mechanical signals emanating from the cell's microenvironment are fundamental regulators of cell behavior and cell adhesions.

One of our goals for this special issue focused on “Cell Adhesive Interactions in Ocular Health and Diseases”, is to present our latest understanding of the role of cell adhesive interactions in physiology and diseases of different ocular tissues including the cornea, lens, trabecular meshwork, and the retina including the retinal pigment epithelium. An additional objective is to emphasize how recent advances have enabled a deeper understanding of the role played by cell adhesive interactions in regulation of ocular tissue functions by both intrinsic and extrinsic signals, how dysregulation of these interactions leads to ocular pathologies, and have provided opportunities for design of novel therapeutics. Finally, we intend to discuss the major gaps in our current understanding of this key area and identify opportunities for further advancement. The interdisciplinary knowledge gained from the various ocular tissues and cell types should be valuable to both eye researchers and other scientific disciplines in the broader context.

Adhesion complexes transduce chemical, mechanical and regulatory signals to control a multitude of cellular activities including proliferation, differentiation, survival, homeostasis, cell shape, migration, gene expression, phagocytosis, barrier function, and stemness. Various intracellular signaling mechanisms regulated by cell adhesive interactions include the Src kinases, focal adhesion kinases, integrin-linked kinase, Rho GTPases and their upstream and downstream regulators, that in turn regulate actin cytoskeletal dynamics. Additionally, mechanotransduction regulated actin cytoskeletal changes influence nucleus stiffness and nuclear actin dynamics and regulate transcriptional programs such as SRF/MRTF and Yap/Taz pathways. We invite submissions in any aspect relevant to cell-matrix or cell-cell adhesions, the effects on cytoskeletal interactions and downstream signaling events.