Ocular Surface Reconstitution

1.1 The ocular surface – anatomy and pathology The corneal epithelium, conjunctival epithelium, and the lacrimal system constitute the ocular surface. A healthy corneal epithelium is essential for corneal health and visual function. The corneal epithelium is a 5to 6-cell-thick layer that provides a defensive barrier against pathologic organisms. It exists in a dynamic equilibrium, with superficial cells being constantly shed into the tear film. Populations of pluripotent stem cells reside in the palisades of Vogt at the human corneoscleral limbus and generate transient amplified cells that centripetally migrate toward the central cornea. These transient amplified cells undergo terminal differentiation into epithelial cells and repopulate the corneal epithelium, i.e. the XYZ hypothesis (Thoft et al., 1983). Severe ocular surface disorders, such as infection, keratoconjunctivitis sicca, Stevens-Johnson syndrome, ocular cicatricial pemphigoid or chemical/thermal injuries, can progress to corneal scarring, conjunctivalization, neovascularization, or stromal melts. Depletion of the limbal stem cells may follow, resulting in impaired vision or eventual corneal blindness. According to the World Health Organization, corneal disorders, e.g. trachoma or onchocerciasis, constitute a significant cause of loss of vision and blindness in the world (Thylefors et al., 1995). The conjunctiva is a thin, transparent, mucus membrane, overlying a thin vascular stroma. It is divided into three geographic zones: bulbar, forniceal, and palpebral. The conjunctival nonkeratinized stratified epithelium contains mucin-producing goblet cells, which are important for tear film stability. Additionally, the conjunctiva participates in the ocular surface antimicrobial defense via the conjunctiva-associated lymphoid tissue, as well as secretory antimicrobial peptides, such as defensins (Haynes et al., 1999). Disorders of the conjunctiva include elastotic changes, fibrovascular proliferation, malignancies, and autoimmune conditions such as Stevens-Johnson syndrome or cicatricial pemphigoid. Complications include dysfunctional tear syndrome, keratinization, symblepharon formation, eyelid disfigurement, and eyelash misalignment. Patient discomfort, cosmetic imperfection, increased risk of infection, and visual impairment are some notable concerns. A normal tear film is essential for maintenance of the corneal and conjunctival epithelia. Composed of three layers, mucin, aqueous and lipid layers, the human tripartite tear film has antimicrobial, epitheliotrophic, mechanical, and optical properties. A wide range of physiologic or pathologic conditions, such as biologic aging, hormonal changes, chemical or thermal injuries, chronic inflammation, or autoimmune disorders, may disrupt the tear film and trigger a deleterious cascade, injuring ocular surface epithelia. Furthermore, suboptimal