Ординатура / Офтальмология / Английские материалы / Dry Eye and Ocular Surface Disorders_Pflugfelder, Beuerman, Elliot Stern_2004
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Figure 7 Limbal stem cell deficiency in patients with (top) Stevens-Johnson syndrome, and (bottom) ocular cicatricial pemphigoid. There is loss of transparency of the cornea, stromal scarring and vascularization, conjunctivalization, cicatricial shortening of the fornices, and symblepheron formation.
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Chronic instability of the corneal epithelium and chronic ulceration may lead to progressive melting of the cornea, with the risk of perforation. Conjunctival epithelial ingrowth of the corneal surface is the pathognomonic feature of limbal stem cell deficiency [5]. Biomicroscopic examination of the cornea reveals a dull and irregular reflex of the cornea, with vascularization and loss of transparency (Fig. 7). Impression cytology confirms conjunctival goblet cells on the surface [83].
Limbal deficiency may be localized (partial) or diffuse (complete) [42,43,45]. In localized limbal stem cell deficiency, some sectors of the limbal and corneal epithelium are normal, and conjunctivalization is restricted to the regions devoid of healthy epithelium. In small, localized areas of limbal deficiency, the disease may remain subclinical with no apparent manifestations, as the proliferative reserve of adjacent healthy limbal tissue may be sufficient to repopulate the corneal surface.
Diagnosis of limbal deficiency is crucial in ocular surface disorders, as these patients are poor candidates for conventional corneal transplantation. Conventional penetrating keratoplasty does not replace corneal stem cells, and hence the corneal graft is subject to complications, with a high risk of rejection. In addition, limbal-deficient eyes are often vascularized, with chronic stromal inflammation, sometimes accompanied by lid margin irregularities and keratinization. Conventional penetrating keratoplasty is therefore prone to failure.
XIII. SUMMARY
1.Stem cells are essential for replenishment of self-renewing tissues such as stratified epithelia.
2.In their dormant state, stem cells have a long life span and replicate infrequently. When proliferation is induced, they give rise to transient amplifying cells, which replicate rapidly. These eventually become postmitotic, and finally, terminally differentiate.
3.Labeling methods that detect slow-cycling cells are often used because specific molecular markers for stem cells have not yet been identified. The great proliferative capacity of stem cells is also an identifying characteristic.
4.As corneal epithelial stem cells proliferate and differentiate during the healing process, they migrate from the limbus and peripheral cornea toward the center.
5.Conjunctival epithelial stem cells originate primarily in the fornix, although pockets of them may be distributed throughout the bulbar and forniceal conjunctiva. They are bipotent, able to differentiate into epithelial or goblet cells.
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6.Limbal stem cell deficiency is characterized by conjunctival epithelial ingrowth of the corneal surface, accompanied by vascularization, goblet cells, and loss of transparency.
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Meibomian Gland Disease
William D. Mathers
Casey Eye Institute, Oregon Health & Science University,
Portland, Oregon, U.S.A
Meibomian glands secrete remarkably diverse components comprising the lipid layer of the tear film. Proper functioning of the glands minimizes evaporation from the tear film. A number of factors may contribute to dysfunction of meibomian glands, often leading to dry eye disease and its characteristic ocular surface inflammation. This chapter reviews the normal anatomy and function of meibomian glands, then considers causes of their dysfunction, the impact of dysfunction on the tear film and ocular surfaces, and treatments for meibomian gland dysfunction.
I.ANATOMY
The meibomian glands lie within the upper and lower lids and fully occupy the tarsal space. Each gland is approximately 1 mm wide and 3–12 mm in length. Some glands branch, but most are essentially a single long cluster of acinar cells, emptying into a central duct.
Meibomian glands develop from a mesenchymal condensation of the frontal nasal and maxillary processes. The ectoderm of the eyelid proliferates in the region of the future upper lid starting at the outer canthus when the fetus is 8–12 mm in length, or at 4–5 weeks. The meibomian (sebaceous and holocrine) gland anlage is first seen at 80 mm as epithelial buds and downgrowths from the basal cells along the lid margins. Arterization of meibomian glands occurs at 5.5 months, or 170 mm, at which time they become situated within the tarsal plates [1,2].
Approximately 20–25 glands are located in the upper lid, and slightly fewer in the lower. The glands of the lower lid are somewhat shorter than in the upper lid, reflecting the size of the tarsal plate. The blood supply to the eyelids
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and subsequently the meibomian glands derives mainly from the ophthalmic and lacrimal arteries by the medial and lateral palpebral branches. Glands are composed of arrays of alveoli, the outer cells of which form a germinal layer (Fig. 1). As the cells mature, they migrate inward toward the center of the alveoli. At maturation, cells laden with secretory substance approach the excretory duct and disintegrate as they release their contents.
Nerve fibers form a plexus around the alveoli. Both the density and number of different neuropeptides suggest that stimulation of the meibomian glands is subject to complex neural control. Human tissue demonstrates the presence of the neuropeptides substance P, vasoactive intestinal peptide (VIP), and calcitonin gene-related peptide (CGRP) [3,4]. Innervation comes to the meibomian glands through the ipsilateral pterygopalatine ganglion and along the more proximal portions of greater petrosal nerve. It appears to be largely parasympathetic, with relatively smaller contributions from sympathetic and sensory sources. Cynomolygus monkey meibomian glands demonstrated axons that stained for neuropeptides SP, CGRP, neuropeptide Y, VIP, the proteins tyrosine hydroxylase, dopamine beta-hydroxylase (DBH), nitric oxide synthase, and NADPH-dehydrogenase.
Figure 1 The normal meibomian gland. As acinar cells mature, they move inward toward the lumen, where they disintegrate and release lipids. Meibomian gland innervation is largely parasympathetic.
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Thus, it appears that various neuropeptides, catecholamines, and nitric oxide may act as neurotransmitter substances to meibomian glands, deriving from the pterygopalatine, superior cervical, and trigeminal ganglia, respectively [5].
II.HORMONE RECEPTORS
While the use of androgen antagonists in human subjects has been shown to alter lipid profiles, there has been disagreement regarding whether androgen receptors are present in human meibomian glands [6]. Meibomian glands are a type of sebaceous gland and therefore are likely to have androgen receptors. Reversetranscription polymerase chain reaction (RT-PCR) studies showed that human meibomian glands contain androgen receptor mRNA, and androgen receptor protein was detected in epithelial cell nuclei [7–9]. However, studies of human tissue by Esmaeli were positive for estrogen receptors but not for androgen receptors [10]. Other animals, including rats, have been studied, often with differing results [11].
III.THE LIPID LAYER: SECRETION, FUNCTIONS, AND COMPOSITION
Normal meibomian secretions slowly emerge from the opening of the ducts along the lid margin. Contraction of the orbicularis muscle applies pressure to the meibomian glands, causing additional lipid to emerge. Forced lid closure intensifies this effect. Lax lids without normal orbicularis activity may have diminished lipid production. Lipid can also be expressed deliberately by direct external pressure to the surface of the lid, or inadvertently by eyelid rubbing.
The lipid layer has multiple functions but serves primarily to decrease evaporation. It is remarkably effective, reducing the evaporation rate to approximately 5% of the rate expected in the absence of a lipid layer [12,13]. Consistent with this, surgical closure of rabbit meibomian gland orifices leads to dry eye, presumably from increased evaporation [14]. The lipid layer also stabilizes the tear film, which helps maintain a smooth optical surface, thus maintaining optimal visual clarity.
The lipid layer is extraordinarily complex, probably containing in excess of 100 distinct lipid compounds, including cholesterol esters, cholesterol, free fatty acids, wax esters, short wax esters, and polar lipids [13,15]. McCulley and Shine have recently proposed a structure for the lipid layer based on this composition [15,16]. The inner sublayer of the lipid layer contains bipolar lipids, whose polar tails interface with the aqueous layer of the tear film, and whose nonpolar outer surfaces interdigitate into the long-chain lipids and sterol esters found in the middle sublayer of the lipid layer. The outer sublayer of the lipid layer,