Ocular Surface Reconstitution
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Introduction 1.1 The ocular surface -anatomy and pathologyThe 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 5-to 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 www.intechopen.comProgress in Molecular and Environmental Bioengineering -From Analysis and Modeling to Technology Applications 292 lacrimal functions may result in poor surgical outcomes, especially after penetrating keratoplasty or limbal stem cell transplantation.Traditionally, the eyelids and lacrimal gland were excluded from the definition of the ocular surface.It is evident that visual function and epithelial health would not be feasible without these structures.The eyelids are essential for ocular surface protection and tear film maintenance.Untreated eyelid deformities, lid malpositions, or eyelash misalignments can precipitate detrimental consequences to the integrity and function of the ocular surface epithelia.Thus, a functional ocular surface requires structurally and functionally intact eyelids and lacrimal gland. Ocular surface reconstitutionIn severe ocular surface disorders, the management strategies entail symptomatic relief, reconstitution of the anatomic and physiologic ocular surface, and treatment and prevention of recurrence of the causative condition.Here we will discuss strategies to restore the conjunctival epithelium, corneal epithelium, and lacrimal function.Figure 1 illustrates the management strategies.Injury or inflammation causes severe ocular surface disorder with conjunctival scarring, limbal stem cell deficiency, corneal opacity with neovascularization, lacrimal dysfunction, disorganized lashes, and lid malposition (a).Mainstay treatment options include antibiotics, anti-inflammatory agents, lubrication, and amniotic membrane transplantation, as well as removal of lashes and correction of lid changes (b).As progress is made in science and tissue bioengineering, tissue replacement and regeneration may be feasible to restore the ocular surface and vision (c). Conjunctival tissue reconstitution 2.1.1 Suppression of cicatricial changesCommonly, ocular surface diseases limited to the conjunctiva progress to excessive cicatricial changes and loss of normal epithelial anatomy.Cicatricial changes to the conjunctival epithelium generally result from poorly controlled fibroblastic activities, e.g.tissue injuries or persistent inflammation.In addition to disrupting the tear film, cicatricialization of the conjunctiva has important implications in glaucoma surgeries, where availablility of healthy conjunctiva is essential for good surgical outcomes.A widely adopted therapeutic strategy is pharmacologic suppression of the inflammatory cascade and the fibroblast activation pathway using corticosteroids and antimetabolites.Recently, research efforts have been directed toward transforming growth factor beta (TGF-) and its involvement in fibroblast proliferation.TGF-is a multifunctional cytokine, which plays an important role in tissue repair and regeneration.After injury, TGF-triggers a complex cascade involving monocyte and leukocyte chemotaxis, induction of angiogenesis, control of production of cytokines and inflammatory mediators, deposition of extracellular matrix materials, and prevention of their enzymatic degradation (Border & Ruoslahti, 1992; Massagué et al., 1992).Excessive TGF-activity has been associated with exuberant fibrotic changes in the eye and other organs.In a murine model, TGF-was associated with formation of granulation tissue (Roberts et al., 1986) and increased inflammatory cell activity, as well as with exuberant extracellular collagen type-III deposition (Siriwardena et al., 1999).Using immunohistochemistry, Razzaque et al (2003) found increased accumulations of type-I and type III collagens and heat shock protein 47, a collagen-binding protein in fibrotic conjunctiva of patients with ocular cicatricial pemphigoid compared to normal subjects.Up-regulation of these proteins was also detected when ex-vivo www.intechopen.comCite
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Literature published during the previous year concerning tumors and tumorlike lesions of the conjunctiva and cornea is reviewed. Conjunctival squamous neoplastic lesions and their association with human papillomavirus are discussed. The role of HMB-45, a monoclonal antibody, in diagnosing conjunctival melanoma is also discussed. Other rare lesions of the cornea and conjunctiva are briefly described. A review of the conjunctival autograft technique for pterygia is presented. Current Opinion in Ophthalmology 1992, 3:431-437
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Five milligrams of fluorouracil was injected subconjunctivally in the rabbit eye, and its concentration changes in the cornea, aqueous humor, and conjunctiva and sclera (both at the injection site and 180 degrees away from it) were determined by microbiological assay. The fluorouracil concentrations in the cornea and the aqueous humor averaged about 20 micrograms/g at one hour. The former decreased to 0.5 micrograms/g at 24 hours, while the latter was 0.03 micrograms/g at ten hours or later. At five hours, the fluorouracil concentrations in the conjunctiva and sclera at the injection site were similar to those 180 degrees away from it, both averaging about 2 micrograms/g. They decreased to 0.3 through 0.9 micrograms/g at 24 hours. The fluorouracil concentrations in the cornea, conjunctiva, and sclera at 24 hours were still above the reported 50% inhibition levels for the cultured conjunctival fibroblast. These findings have potential clinical implications for the safe use of fluorouracil.
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To determine the requirement of IkappaB kinase alpha (Ikkalpha) for differentiation of the mammalian cornea and conjunctiva.Newborn mice or surgically removed embryonic day (E)18 to E19 fetuses of wild-type and IKK:alpha(-/-) mice were analyzed by light microscopy and electron microscopy or immunocytochemistry using anti-keratin (K)12, K4, K5, IkappaB, or nuclear factor (NF)-kappaB (p50) antibody.In the IKKalpha(-/-) eyes, the epithelium of the cornea and the conjunctiva consisted of poorly differentiated cells with round nuclei. K5 was much stronger in the conjunctiva of the IKKalpha(-/-) mice. Expression of K12 in the cornea and K4 in the conjunctiva was impaired in the IKKalpha(-/-) mice. IkappaB expression was low in epithelium of the cornea and conjunctiva of the wild type mice but was very strong in that of the IKKalpha(-/-) mice. During normal development of the conjunctiva, nuclear localization of p50 was seen in areas where basal undifferentiated cells give rise to differentiated cell types, marked by expression of cK4. However, in the IKK++alpha(-/-) tissues, no nuclear p50 staining was detected.IKKalpha is specifically required for formation of cornea and conjunctiva. This function may be exerted through an effect on NF-kappaB activity.
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A pterygium is nothing but a fold of ocular conjunctiva drawn over and fastened to the cornea, and to make our operation for pterygium a permanent success, we must after releasing the conjunctival fold from the cornea, arrange matters so that the conjunctiva cannot be drawn back over the cornea again. In a pterygium of moderate size this aim is usually attained by a very simple operation. The conjunctival fold is carefully dissected from the cornea, and allowed to retract as far as it will, from the corneal margin. This leaves between the retracted conjunctiva and the cornea, a small wound area to close which we draw the conjunctiva from above and below together, and unite the edges by two sutures. If this wound heals by first intention, there is no danger of a recurrence of the pterygium. But in a number of cases the pterygium is so large, and
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The paper presents a case of a 44 years old man, K.Z., with an invasive carcinoma of cornea and conjunctiva of his left eye. The patient was hospitalized for the first time eight years ago due to a viral keratitis of this eye, afterwards for three times due to changes within his cornea and conjunctiva in form of a cauliflower-like whitepink small tumour at the conjunctiva-cornea border line. During his last hospitalization the change covered two thirds of the cornea and it was going over onto the bulbar conjunctiva. The fourfold cytological and histopathological assays of the change did not show carcinomatous cells, but only cells of multi-layer, flat epithelium with features of excessive cornification. It is only the last histopathological assay of the cut-off small tumour that showed that it was carcinoma planoepitheliale keratodes invasivum. The consultant radiologists recommended removing the eye bulb since high radiation doses, which would be necessary, would destroy the eye bulb and yield postradiation reactions. The histopathological assays of the enucleated eye bulb confirmed the diagnosis and showed the superficial infiltration of the conjuctiva border. The patient was subjected to the X-ray treatment over the conjunctival sac region.
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The anterior segment of the eye ball, i. e., cornea and conjunctiva, serves as the barrier to the external stimuli. Cornea is transparent and is a "window" of the light sense, while conjunctiva covers the sclera, the main part of the eyeshell. Fibrosis/scarring in cornea potentially impairs vision by the reduction of its transparency and the alteration of the regular curvature. Fibrotic reaction in conjunctiva is also of clinical importance because inflammatory fibrosis in this tissue affects the physiology of the cornea and also a problem of post-eye surgery. In this review, we discuss the topic that is quite critical in vision. Although, various growth factors have been considered to be involved in, focus was put on the roles of transforming growth factor β (TGFβ).
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