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Cultured Cells for Corneal Endothelial Therapy

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Modern Keratoplasty

Part of the book series: Essentials in Ophthalmology ((ESSENTIALS))

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Abstract

The human cornea is a five-layered tissue that provides two-thirds of the total refractive power of the eye, and it is the first barrier protecting the intraocular content. The corneal endothelium, the inner layer, is in charge of maintaining the cornea in a relatively dehydrated state and therefore transparent. The endothelial cell layer failure leads to corneal swelling, loss of transparency and blindness.

Currently, the only effective and probed way to restore endothelial function universally is to perform an allogenic graft. Since Melles revolutionized the field by describing a method to dissect only Descemet Membrane (DM) from the recipient eye, leaving the posterior lamella intact, and after Price and Gorovoy pioneered Descemet stripping endothelial keratoplasty (DSEK), a variety of endothelial keratoplasty techniques have taken over. However, there is a scarcity of donors to adequate to high and increasing demand.

Cell culture techniques make it possible to expand ex vivo the corneal endothelial cells (CEC) to subsequently inject a cell solution into the anterior chamber, or else to manufacture constructs made up of acellular corneal stroma, acellular Descemet membrane or carriers manufactured by tissue bioengineering, and colonized by CEC expanded ex vivo, which could then be grafted onto the recipient. Nowadays, we are in an outstanding position to develop corneal endothelial cell sheets for endothelial keratoplasty: reproducible and well-defined culturing methods and conditions have been achieved in the last decades. Regardless of advances in promoting human CEC proliferation, the achieved capacity for expanding human CECs is still highly limited; new sources of CECs are therefore sought. The use of extraocular cells capable of differentiating into corneal endothelial cells is highly desirable. Recent advances have been achieved in differentiation protocols from embryonic stem cells and adipose-derived mesenchymal stem cells.

New advances in biomimetic materials and manufacturing protocols such as electrospinning, nanolithography, vitrification, and advances in novel 3D printing techniques such as LIFT, laser-assisted bioprinting, and others will aid in the search for a donor-independent biocompatible carrier.

Further development of these and previous approaches, by defining the growth factors, the signaling pathways implicated in directed differentiation, the use of more practical cells to derive hCECs, and the in vivo demonstration of functionality are urgently needed.

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Authors and Affiliations

  1. Cell Engineering Laboratory, La Paz University Hospital Health Research Institute, IdiPAZ, Madrid, Spain

    M. P. De Miguel, M. Cadenas Martín & A. Moratilla

  2. IRYCIS, Ophthalmology Department, Ramón y Cajal University Hospital, Madrid, Spain

    F. Arnalich-Montiel

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  1. M. P. De Miguel
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  2. M. Cadenas Martín
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  3. A. Moratilla
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  1. Vissum Miranza, Miguel Hernández University, Alicante, Spain

    Jorge L. Alió

  2. Vissum-Instituto Oftalmologico de Alica, Miguel Hernandez University, Alicante, Alicante, Spain

    Jorge L. Alió del Barrio

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De Miguel, M.P., Cadenas Martín, M., Moratilla, A., Arnalich-Montiel, F. (2023). Cultured Cells for Corneal Endothelial Therapy. In: Alió, J.L., del Barrio, J.L.A. (eds) Modern Keratoplasty. Essentials in Ophthalmology. Springer, Cham. https://doi.org/10.1007/978-3-031-32408-6_36

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