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Adv Healthc Mater. 2016 Nov;5(22):2896-2910. doi: 10.1002/adhm.201600848. Epub 2016 Oct 4.

In Vitro Topographical Model of Fuchs Dystrophy for Evaluation of Corneal Endothelial Cell Monolayer Formation.

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Department of Biomedical Engineering, National University of Singapore, Singapore, 117583.
Institute of Materials Research and Engineering, Agency for Science, Technology and Research (A*STAR), Singapore, 138634.
Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute, Singapore, 169856.
Duke-NUS Graduate Medical School, Singapore, 169857.
Singapore National Eye Centre, Singapore, 168751.
Department of Surgery, National University of Singapore, Singapore, Mechanobiology Institute, National University of Singapore, Singapore, 117411.
Department of Chemical Engineering, University of Waterloo, Waterloo, Ontario, Canada, N2L 3G1.


A common indication for corneal transplantation, which is the most transplanted tissue, is a dysfunctional corneal endothelium due to Fuchs' endothelial dystrophy (FED). FED is diagnosed by the presence of in vivo pathological microtopography on the Descemet membrane, which is called corneal guttata. Minimally invasive corneal endothelial cell regenerative procedures such as endothelial cell injection therapy and Rho kinase inhibitor pharmacotherapy have been proposed as alternatives to conventional corneal transplantation for FED patients. However, the effect of guttata on monolayer reformation following such therapies is unknown and there is no equivalent in vitro or animal model to study monolayer reformation. Using a synthetic guttata FED disease model, the formation of the monolayer is investigated to evaluate the efficacy of both therapies. Results obtained suggest that guttata dimensions, density, and spacing greatly affect the fate of corneal endothelial cells in terms of migratory behavior and monolayer reformation. Densely packed synthetic guttata mimicking late-stage FED hinders monolayer reformation, while synthetic guttata of lower height and density show improved monolayer formation. These results suggest that severity of the FED, as determined by height and density of existing guttata, can potentially attenuate corneal endothelial monolayer formation of corneal cell injection therapy and pharmacotherapy.


Fuchs dystrophy; biomimetic guttata; cell migration; cell therapy; corneal endothelium

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