Use of keratin biopolymer films for reconstruction of the ocular surface

Severe ocular surface scarring can be found in many ocular surface disorders such as ocular membrane pemphigoid, Stevens-Johnson syndrome and chemical/thermal burns. Fornix shortening, symblepharon and finally ankyloblepharon formation can be the clinical consequence. The cicatrisation of the fornices, especially the inferior fornix, causes entropion and trichiasis, which continually damages the ocular surface epithelia and results in recurrent erosions of the cornea, ulcer formation and secondary bacterial infection (Ormerod et al., 1988). Also, disturbed integrity of the tear film and dry eye symptoms can occur due to ineffective blinking, reduction of the tear meniscus, loss of goblet cells and keratinisation of the ocular surface epithelia (Ralph, 1975; Solomon et al., 2003).

In these patients, reconstructions of the conjunctiva and the corneal surface have to be performed. The functions of the cornea and conjunctiva are complex and therefore a substitute tissue needs to meet several criteria.

The advantages of autologous tissues such as conjunctiva and oral or nasal mucosa are evident as they contain an appropriate matrix with epithelium and do not stimulate rejection. However, this strategy is limited by the lack of suitable donor tissue and also in terms of corneal surface replacement by a lack of transparency. Also these tissues may be impaired in patients suffering from autoimmune cicatrising disease.

Amniotic membrane is frequently used for transplantation onto the ocular surface and it has also been shown to be a suitable substrate for the culture of corneal and conjunctival epithelial cells. However, the results with amniotic membrane grafts for ocular surface reconstruction in the presence of chronic inflammatory ocular surface disease are not satisfactory (Henderson and Collin, 2008; Solomon et al., 2003) and other problems with the use of AM include reliable supply of membranes, limited transparency, costly screening, risk of disease transmission and considerable biological variations between donors (Levis et al., 2010). Therefore, there is a need for the development of new corneal and conjunctival substitutes, which are biocompatible, have low variation in quality, are suitable as a matrix for ocular surface epithelial cells, biomechanically stable over a long period on the ocular surface and safe for the use in humans.

Our previous studies have shown the successful use of keratin based matrices for corneal surface reconstruction in vitro and in vivo as well as the successful use of plastic compressed collagen matrices as a matrix for conjunctival replacement. The aim of this project is to further improve these constructs for corneal and conjunctival replacement to specifically address certain clinical problems in ocular surface reconstruction, namely, persistent epithelial defects, corneal neovascularization and scarring. Based on the results of our previous studies we investigate the suitability of keratin film based matrices and PC collagen gel based cell sheets containing different substances for corneal and conjunctival surface reconstruction in vitro using various functional assays, cell biology and molecular biology methods and in vivo using an established animal model.

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