March 2015
Volume 56, Issue 3
Research Highlight  |   March 2015
Dynamic Studies of Human Corneal Fibroblasts
Author Affiliations
  • Andrew J. Quantock
    School of Optometry and Vision Sciences, Cardiff University, Cardiff, Wales, United Kingdom;
Investigative Ophthalmology & Visual Science March 2015, Vol.56, 2091. doi:10.1167/iovs.15-16836
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      Andrew J. Quantock; Dynamic Studies of Human Corneal Fibroblasts. Invest. Ophthalmol. Vis. Sci. 2015;56(3):2091. doi: 10.1167/iovs.15-16836.

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      © ARVO (1962-2015); The Authors (2016-present)

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Keratocytes ordinarily exist in a quiescent state. However, following injury or after surgery they become activated and fibroblastic and drive the repair of the corneal matrix, a process that is highly dynamic and occurs in three dimensions (3D). Previously, Miron-Mendoza and associates1 used time-lapse microscopy to study the migration of human corneal fibroblasts out of compressed extracellular matrix constructs into a surrounding uncompressed 3D matrix of either collagen or fibrin. This showed that cells migrated individually into collagen matrices (where they subsequently formed connections), but as small groups into fibrin matrices. In their current study, Miron-Mendoza et al.2 further demonstrate that cells migrate separately into uncompressed 3D collagen matrices even in the presence of thrombin, which they had found to induce cell clustering in 2D on compliant, but not rigid, collagen matrices. The authors also discovered that cells migrating into fibrin moved collectively and formed an interconnected network, even when the cytoskeleton was perturbed by the Rho kinase inhibitor Y-27632 and/or the myosin II inhibitor blebbistatin. The results elegantly demonstrate how time-lapse microscopy helps elucidate the integrated, dynamic behavior of corneal fibroblasts in 3D, and the videos of this make compelling viewing. As the authors point out, the interplay between cells, and their interaction with their environment, are important for corneal wound healing, tissue engineering, and development. Keratocytes do not exist in isolation but form highly extended networks, and the work of Miron-Mendoza and colleagues has provided extra insights into the dynamic nature of cell–cell connectivity. Previously, Nishida and colleagues3 beautifully documented an integrated system of long, thin cytoplasmic cell processes in the corneas of young adult rats seen by scanning electron microscopy (SEM). More recently, Young and coworkers4 used a serial block face ablative 3D SEM approach and found that long, thin cell protrusions of presumptive keratocytes in developing cornea extended large distances into the extracellular space, connecting with each other and mirroring (perhaps dictating) the alignment of collagen bundles and emergent lamellae. These studies, however, are merely “snapshots in time,” and the work of Miron-Mendoza and associates significantly adds to the field in the quest for a more comprehensive appreciation of corneal cell–cell and cell–matrix interactions. 
Miron-Mendoza M, Lin X, Ma L, Ririe P, Petroll WM. Individual versus collective fibroblast spreading and migration: regulation by matrix composition in 3D culture. Exp Eye Res. 2012; 99: 36–44.
Miron-Mendoza M, Graham E, Kivanany P, Quiring J, Petroll WM. The role of thrombin and cell contractility in regulating clustering and collective migration of corneal fibroblasts in different ECM environments. Invest Ophthalmol Vis Sci. 2015; 56: 2079–2091.
Nishida T, Yasumoto K, Otori T, Desaki J. The network structure of corneal fibroblasts in the rat as revealed by scanning electron microscopy. Invest Ophthalmol Vis Sci. 1988; 29: 1887–1890.
Young RD, Knupp C, Pinali C, et al. Three-dimensional aspects of matrix assembly by cells in the developing cornea. Proc Natl Acad Sci U S A. 2014; 111: 687–692.

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