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Eyelid Secretions and the Prevention and Production of Disease

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Eyelid Secretions and the Prevention and Production of Disease Eye (1988) 2, 164-171 Eyelid Secretions and the Prevention and Production of Disease A. J. BRON Oxford Summary Tears are necessary for the continued health of the ocular surface. Normal con­ stitutents include water, mucin, and lipids, electrolytes, non-electrolytes, and pro­ teins. Lacrimal secretion is under cholinergic control and modulated by sympathetic adrenergic, peptidergic (VIP) and humoral influences; the meibomian glands are innervated, but the goblet cells are not. Retinoids are important for ocular health �nd prealbumen may be a carrier for vitamin A in the tears to supply corneal epithelium with its requirements. Changes in tear constituents may cause certain ocular disorders. In dry eyes increased osmolarity is thought to cause surface ocular damage but the presence of granulocytes and inflammatory mediators such as prostaglandins and super-oxide may contribute to inflammatory events in this and other external diseases. It has long been accepted that tears are neces­ evaporation and exchange across the ocular sary for the continued health of the ocular surface. surface, maintaining the non-keratinised sur­ Wolff's basic 3 layer model for the tear film face essential for corneal transparency and still holds today in modified form. The bulk of lubrication required for movement of lid on the tears are water, the surface bears a lipid globe. It is a more recent concept that changes coat and mucin is present in the aqueous in the tear constituents might not only be a phase; however the disposition at the surface reflectionof surface eye disease, but a cause of of the eye is still in question. some of its manifestations. Lacrimal fluid secretion by the lacrimal The normal eye is bathed with tears, com­ gland is under neural control of the parasym­ prising lacrimal fluid of lacrimal and accessory pathetic system via cholinergic fibres, which lacrimal origin to which components of con­ synapse in the pterygopalative ganglion.s junctival and lid origin are added. Tear flow Secretion is modulated by adrenergic sympa­ has been estimated variously as 0.3 fd/mml or thetic stimulation by its action on the vascular 1.2 f..tllmm.2 Reflex secretion is present at supply. Lacrimal gland cells also secrete in birth, though it is said that emotional tears response to agonists and therefore, presum­ have their onset at about 3 months of life.3 ably to circulating adrenaline.6•7 The gland Baum has suggested that so-called basal tears also receives peptidergic innervation by vaso­ are really reflex in nature and that all intestinal peptide (VIP) 8-10 and substance :P measured flow is a response at least to some (SP) immuno-reactive fibres.ll•12 Cholinergic environmental stimulus. In his view basal flow and VIP fibres do not innervate the same is negligible. Tear flow can be amplified over receptors, but cholinergic and, adrenergic one hundred-fold in response to irritation.4 pathways probably converge on the same Tear fluid losses are by bulk lacrimal drainage, second messenger system in the cell, indepen- Correspondence to: Nuffield Laboratory of Ophthalmology, Walton Street, Oxford OX2 6AW. EYELID SECRETIONS AND THE PREVENTION AND PRODUCTION Of DISEASE 165 dent of that for VIP.9 Humoral factors also delivered to the conjunctiva by the con­ influence secretion, so that the glandular junctival vessels and there is presumably the secretions in vivo and in vitro are dependent same sequence of retinol carriage by plasma on stimulation by androgens, oestrogens, retinol binding protein (RBP) with delivery to glucagon ACTH and melanocyte stimulating a cellular RBP, that exists for other epithelial 2 hormonesl which influence not only aqueous tissues. For the cornea, which is avascular, and protein production but also glandular another mode of delivery may exist, via the size. The lacrimal gland is generally larger in tears. Vitamin A is present in the tears, the male. In the rat,14 Allansmith and others secreted by the lacrimal gland. 22 Recently, demonstrated an equal rate of development Chao and Butala have suggested that tear­ up to the age of puberty (2. 5-5. 5 weeks) after specific prealbumen, which is present in sub­ which area and density of acini increased in stantial quantities in the tears, is a binding males only. Perifused female rat lacrimal protein concerned with retinol carriage in the glands secrete less proteins in response to tears and important for the delivery of vitamin phenylephrine than males, a difference A to the corneal epithelium. 23 This is in keep­ reduced by oophorectomy. IS Oestradiol ing with the studies of Thoft and his colleagues receptors have been demonstrated on lacri­ who have demonstrated the transdifferentia­ mal acini in various species. In rabbit, tion of conjunctival epithelial into corneal oophorectomy is followed by acinar degener­ epithelial cells, with loss of tear goblet popula­ ation and massive lymphocyte infiltration.16 In tion, after resurfacing a total corneal defect by the rat, tear volume is increased by orchidec­ the former cell type. 24.25 Conversely, this tomy, an effect blocked by hypophysectomy, transdifferentiation does not occur if the con­ but not by thyroidectomy, adrenalectomy or junctival cells re-surface vascularised cornea, oestrogen administration. 17 Interactions are presumably because of the higher levels of evidently complex and probably species retinol delivered to the re-surfacing cells in dependent. This is likely to be of relevance to this situation. 26.27 age related-changes occurring in the lacrimal The table below shows the major categories gland, particularly in the menopause in of tear components. Their role in the preven­ women. tion and production of disease is now Surface tear oils are derived from the oil discussed. glands of the lids; these are holocrine in nature and secretion onto the lids can be explained as Table. Constituents of the Normal Tears the result of continuous synthesis and release with breakdown of glandular acini. The ana­ Water lagous sebaceous glands of the skin are Lipids: Meibomian; mucin associated. affected by levels of sex hormones. 18 Mucins: Goblet cell; other? Recently, it has been demonstrated that the Electrolytes meibomian glands receive a rich peptidergic Non-electrolytes: Glucose; lactate; amino-acids; urea innervation (VIP and SP) for which a neu­ Proteins: (a) Albumin: pre-albumin (b) Enzymes: Lysozyme; peroxidase; roregulatory role must be considered. 19 various glycosidases Mucin is secreted by the goblet cells of the (c) Proteases: plasminogen activators conjunctiva, and mucus glycoprotein has (d) Anti proteases: (XI anti-trypsin; (Xl been immunoidentified in human goblet cells macro globin (e) Immunoglobulins: IgA, G, E; using antibody against purified mucin frac­ Mediators: Prostaglandins; histamine; complement; tions. These fail to label lacrimal gland. 20'z1 O2 (?) The goblet cells are not innervated, but in Radical Scavengers: Ascorbate; lactoferrin; cerulo­ other parts of the body respond to humoral plasmin anti-complement stimulation by secretin, serotonin, and prosta­ Other materials: Catecholamines; endorphins PGD). glandins (PGE2 and Retinol is essen­ tial to maintain the ocular surface in its non­ keratinised state and maintain goblet-cell Electrolytes: Tear sodium concentration density within the conjunctiva. Retinol is approximates that of the plasma. This value 166 A. J. BRON does not represent that of lacrimal fluid as Surprisingly, few reliable studies of tear secreted since sodium is pumped back across sodium concentration have been made in dry the cornea at least, in exchange for chloride eyes. 30 Studies by Mengher in Oxford, have ions, and further modification of con­ shown a small but significant increase in tear centration arises as a result of evaporation on sodium compared to normal tears. This is in lid opening. The tears are secreted slightly keeping with studies of tear osmolarity since hypotonic and become hypertonic. Potassium electrolytes make the major contribution to levels are about four times those of the the osmolarity of the body fluids. It is puzzling plasma, perhaps, by analogy to the situation that such a rise, attributable to hypercon­ in the salivary glands, as a result of secretion centration of tears, is not shown by tear of potassium across the lacrimal ductules. It is potassium. of interest that ocular surface cells are able to Gilbard et al demonstrated in a series of tolerate this high external potassium con­ studies that tear osmolarity is increased in dry centration, which would be lethal to cells eye. 3l This has been reproduced experi­ exposed to the plasma or extracellular fluid. mentally in the rabbit and rat, with the pro­ Manganese is also present in tears in a con­ duction, in some32 but not a1l33 studies, or centration which greatly exceeds plasma surface signs. Gilbard et al have shown that levels; Tapazo originally found levels of one cultured rabbit corneal epithelial cells are thousand fold higher28 while Frey found a 30 damaged by hyperosmolar saline. 34 Their fold difference. 3 Frey has noted the critical studies showed normal tears to have a mean role of the 'salt glands' of the seagull and other osmolarity of 302 mOsm/L while dry eye tears birds as an excretory organ, concerned like showed an average increase of 41 mOsm/L. the kidney in mammals, in electrolyte regu­ As a diagnostic test, a cut off value of 312 lation. He has proposed a similar, though lim­ mOsm/L had a sensitivity of 76 per cent and ited, role, for the lacrimal glands in other specificity of 84 per cent. 35 species including man. He has also suggested The tear mucins (mucous glycoproteins) that excretion of manganese in copious emo­ are responsible for the high relative viscosity tional tears, could influence the emotional of tears (2. 92).36 Their origin from goblet cells state, since this ion has an important function has been proved conclusively in humans, by affecting mood.
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