gms | German Medical Science

In comparison to the other vertebrate tissues, the morphology of the eye cornea appears to be uncomplex. The cornea is avascular and the tissue is provided with metabolic energy, e.g. glucose and oxygen, through limbal circulation, aqueous liquor as well as film. However, the cornea has to accomplish complex functions, not only to protect the eye and concomitantly to allow light to transmit, but also to support the structural and functional organization of the extracellular fibrillar reticulation into which the keratocytes are embedded, as well as the dense and compact network of nerve endings is several hundred-fold greater than that of the skin. The bioenergetic needs, just to maintain the functional conditions and activities of the ATP hydrolases, involved in the interactions of the cell junctions of the epithelium and endothelium which are bordering the stroma, and the membrane potential of the nerve terminals are huge. The regeneration capacity of the cornea is low, also due to the slow cycling cell rate of the limbal stem cells that give rise to the corneal epithelial cells. In turn, impairment of cornea often requires the transplantation of donated corneal tissue/grafts of different coverage, ranging from penetrating keratoplasty to lamellar keratoplasty. Worldwide approximately 300 million individuals suffer from visual impairment, of which 40 million patients are blind.

Even though grafting of donor cornea is a sufficiently established technique and frequently applied, like at the University Medical Center/Cornea Bank of Rhineland-Palatine, Mainz Germany, donor corneas are only insufficiently available. Therefore, alternatives to donor corneas have to be developed. Principally, two routes had been followed to reduce this problem, FIRST the design and development of prosthetic corneas, the keratoprostheses, with the Boston- as well as the osteo-odonto-type of prostheses as examples, and SECOND decellularized animal corneas, e.g. porcine corneas. Allografting as well as xenografting approaches are, to some extent, promising in cornea transplantation, due to the restricted immune defense capacity of the cornea.

Fibrillar collagen, the major organic component in the cornea, controls not only the transmission of visible light but also the attachment and patterning of the cells in this tissue. One of the important characteristics of collagen is its unique posttranslational modifications, especially the covalent intermolecular cross-linking. The enzyme-mediated cross-linking, mediated by lysyl oxidase, is crucially dependent on the extent of hydroxylation of specific lysine (Lys) residues in the collagen molecule as well as the extent of oxidative deamination of the Lys and hydroxylysine (Hyl). In addition, the glycosylation pattern at helical Hyl residues, involved in cross-linking, modulate the maturation of collagen cross-links. Artificial cross-linking of proteins or also collagen with EDC [1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide] results in the formation of an amide or ester bond, with some minor unwanted side reactions, e.g. a rearrangement to stable N-acylurea.

In our approach we use silica-based as well as polyphosphate-based biopolymers (Figure 1 [Fig. 1]) to fabricate transparent cornea with the required mechanical stabilities. First examples will be presented.