Sex hormones and the dry eye

Clinical and Experimental Optometry

Volumn 97, Issue 4, 2014, Pages 324-336

  Truong, Susan ^a   Cole, Nerida ^a,b   Stapleton, Fiona ^a   Golebiowski, Blanka ^a  

^a UNIVERSITY OF NEW SOUTH WALES   (Australia)

^b UNIVERSITY OF TECHNOLOGY SYDNEY   (Australia)

Author keywords

Androgen; Dry eye; Dry eye treatment; Lacrimal gland; Meibomian gland; Ocular surface; Oestrogen; Progesterone; Sex hormones; Sex steroids; Testosterone

Indexed keywords

SEX HORMONE;

CHEMISTRY; DRY EYE SYNDROMES; FEMALE; HORMONE SUBSTITUTION; HUMAN; LACRIMAL FLUID; MALE; METABOLISM; PROCEDURES;

DRY EYE SYNDROMES; FEMALE; GONADAL STEROID HORMONES; HORMONE REPLACEMENT THERAPY; HUMANS; MALE; TEARS;

EID: 84925545865     PISSN: 08164622     EISSN: 14440938     Source Type: Journal    
DOI: 10.1111/cxo.12147     Document Type: Review

References (208)

1. Dursun D, Monroy D, Knighton R, Tervo T, Vesaluoma M, Carraway K, Feuer W et al. The effects of experimental tear film removal on corneal surface regularity and barrier function. Ophthalmology 2000; 107: 1754-1760.
2. Goto E, Yagi Y, Matsumoto Y, Tsubota K. Impaired functional visual acuity of dry eye patients. Am J Ophthalmol 2002; 133: 181-186.
3. Lemp MA. Report of the National Eye Institute/Industry workshop on clinical trials in dry eyes. Eye Contact Lens 1995; 21: 221-232.
4. Dartt DA. Regulation of tear secretion. Adv Exp Med Biol 1994; 350: 1-9.
5. Rolando M, Zierhut M. The ocular surface and tear film and their dysfunction in dry eye disease. Surv Ophthalmol 2001; 45: S203-S210.
6. Barabino S, Dana M. Dry eye syndromes. Chem Immunol Allergy 2007; 92: 176-184.
7. Pflugfelder SC. Antiinflammatory therapy for dry eye. Am J Ophthalmol 2004; 137: 337-342.
8. Research in dry eye: report of the Research Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007; 5: 179-193.
9. Stern ME, Beuerman RW, Fox RI, Gao J, Mircheff AK, Pflugfelder SC. The pathology of dry eye: The interaction between the ocular surface and lacrimal glands. Cornea 1998; 17: 584-589.
10. Stern ME, Beuerman RW, Fox RI, Gao J, Mircheff AK, Pflugfelder SC. A unified theory of the role of the ocular surface in dry eye. Adv Exp Med Biol 1998; 438: 643-651.
11. Johnson ME, Murphy PJ. Changes in the tear film and ocular surface from dry eye syndrome. Prog Retin Eye Res 2004; 23: 449-474.
12. Li D-Q, Luo L, Chen Z, Kim H-S, Song XJ, Pflugfelder SC. JNK and ERK MAP kinases mediate induction of IL-1beta, TNF-alpha and IL-8 following hyperosmolar stress in human limbal epithelial cells. Exp Eye Res 2006; 82: 588-596.
13. Luo L, Li D-Q, Doshi A, Farley W, Corrales RM, Pflugfelder SC. Experimental dry eye stimulates production of inflammatory cytokines and MMP-9 and activates MAPK signaling pathways on the ocular surface. Invest Ophthalmol Vis Sci 2004; 45: 4293-4301.
14. Suzuki T, Schirra F, Richards SM, Jensen RV, Sullivan DA. Estrogen and progesterone control of gene expression in the mouse meibomian gland. Invest Ophthalmol Vis Sci 2008; 49: 1797-1808.
15. Sullivan DA, Jensen RV, Suzuki T, Richards SM. Do sex steroids exert sex-specific and/or opposite effects on gene expression in lacrimal and meibomian glands? Mol Vis 2009; 15: 1553-1572.
16. Azzi L, El-Alfy M, Labrie F. Gender differences and effects of sex steroids and dehydroepiandrosterone on androgen and oestrogen alpha receptors in mouse sebaceous glands. Br J Dermatol 2006; 154: 21-27.
17. Suzuki T, Sullivan DA. Estrogen stimulation of proinflammatory cytokine and matrix metalloproteinase gene expression in human corneal epithelial cells. Cornea 2005; 24: 1004-1009.
18. Pfeilschifter J, Koditz R, Pfohl M, Schatz H. Changes in proinflammatory cytokine activity after menopause. Endocr Rev 2002; 23: 90-119.
19. Richards SM, Jensen RV, Liu M, Sullivan BD, Lombardi MJ, Rowley P, Schirra F et al. Influence of sex on gene expression in the mouse lacrimal gland. Exp Eye Res 2006; 82: 13-23.
20. Sato EH, Sullivan DA. Comparative influence of steroid hormones and immunosuppressive agents on autoimmune expression in lacrimal glands of a female mouse model of Sjögren's syndrome. Invest Ophthalmol Vis Sci 1994; 35: 2632-2642.
21. Calonge M. The treatment of dry eye. Surv Ophthalmol 2001; 45: S227-S239.
22. Nelson JD, Helms H, Fiscella R, Southwell Y, Hirsch JD. A new look at dry eye disease and its treatment. Adv Ther 2000; 17: 84-93.
23. Schaumberg DA, Sullivan DA, Buring JE, Dana MR. Prevalence of dry eye syndrome among US women. Am J Ophthalmol 2003; 136: 318-326.
24. Caffery BE, Richter D, Simpson T, Fonn D, Doughty M, Gordon K. The Canadian Dry Eye Epidemiology Study. Adv Exp Med Biol 1998; 438: 805-806.
25. Schaumberg DA, Dana R, Buring JE, Sullivan DA. Prevalence of dry eye disease among US men: estimates from the Physicians' Health Studies. Arch Ophthalmol 2009; 127: 763-768.
26. McCarty CA, Bansal AK, Livingston PM, Stanislavsky YL, Taylor HR. The epidemiology of dry eye in Melbourne, Australia, historical image. Ophthalmology 1998; 105: 1114-1119.
27. Albietz JM. Prevalence of dry eye subtypes in clinical optometry practice. Optom Vis Sci 2000; 77: 357-363.
28. Chia E-M, Mitchell P, Rochtchina E, Lee AJ, Maroun R, Wang JJ. Prevalence and associations of dry eye syndrome in an older population: the Blue Mountains Eye Study. Clin Exp Ophthalmol 2003; 31: 229-232.
29. Sullivan DA, Wickham LA, Rocha EM, Krenzer KL, Sullivan BD, Steagall R, Cermak JM et al. Androgens and dry eye in Sjögren's syndrome. Ann N Y Acad Sci 1999; 876: 312-324.
30. Sullivan DA, Belanger A, Cermak JM, Berube R, Papas AS, Sullivan RM, Yamagami H et al. Are women with Sjögren's syndrome androgen-deficient? J Rheumatol 2003; 30: 2413-2419.
31. Cermak JM, Krenzer KL, Sullivan RM, Dana MR, Sullivan DA. Is complete androgen insensitivity syndrome associated with alterations in the meibomian gland and ocular surface? Cornea 2003; 22: 516-521.
32. Sullivan BD, Evans JE, Cermak JM, Krenzer KL, Dana MR, Sullivan DA. Complete androgen insensitivity syndrome: effect on human meibomian gland secretions. Arch Ophthalmol 2002; 120: 1689-1699.
33. Smith JA, Vitale S, Reed GF, Grieshaber SA, Goodman LA, Vanderhoof VH, Calis KA, Nelson LM. Dry eye signs and symptoms in women with premature ovarian failure. Arch Ophthalmol 2004; 122: 151-156.
34. Pflugfelder SC. Hormonal deficiencies and dry eye. Arch Ophthalmol 2004; 122: 273-274.
35. Yavas GF, Ozturk F, Kusbeci T, Ermis SS, Yilmazer M, Cevrioglu S, Aktepe F et al. Meibomian gland alterations in polycystic ovary syndrome. Curr Eye Res 2008; 33: 133-138.
36. Srinivasan S, Joyce E, Senchyna M, Simpson T, Jones L. Clinical signs and symptoms in post-menopausal females with symptoms of dry eye. Ophthalmic Physiol Opt 2008; 28: 365-372.
37. Mathers WD, Stovall D, Lane JA, Zimmerman MB, Johnson S. Menopause and tear function: the influence of prolactin and sex hormones on human tear production. Cornea 1998; 17: 353-358.
38. Versura P, Campos EC. Menopause and dry eye. A possible relationship. Gynecol Endocrinol 2005; 20: 289-298.
39. Versura P, Fresina M, Campos EC. Ocular surface changes over the menstrual cycle in women with and without dry eye. Gynecol Endocrinol 2007; 23: 385-390.
40. Vavilis D, Maloutas S, Nasioutziki M, Boni E, Bontis J. Conjunctiva is an estrogen-sensitive epithelium. Acta Obstet Gynecol Scand 1995; 74: 799-802.
41. Kramer P, Lubkin V, Potter W, Jacobs M, Labay G, Silverman P. Cyclic changes in conjunctival smears from menstruating females. Ophthalmology 1990; 97: 303-307.
42. Erdem U, Ozdegirmenci O, Sobaci E, Sobaci G, Göktolga U, Dagli S. Dry eye in post-menopausal women using hormone replacement therapy. Maturitas 2007; 56: 257-262.
43. Schaumberg DA, Buring JE, Sullivan DA, Dana MR. Hormone replacement therapy and dry eye syndrome. JAMA 2001; 286: 2114-2119.
44. Uncu G, Avci R, Uncu Y, Kaymaz C, Develioglu O. The effects of different hormone replacement therapy regimens on tear function, intraocular pressure and lens opacity. Gynecol Endocrinol 2006; 22: 501-505.
45. Gurwood AS, Gurwood IO, Gubman DT, Brzezicki LJ. Idiosyncratic ocular symptoms associated with the estradiol transdermal estrogen replacement patch system. Optom Vis Sci 1995; 72: 29-33.
46. Sullivan BD, Evans JE, Krenzer KL, Dana RM, Sullivan DA. Impact of antiandrogen treatment on the fatty acid profile of neutral lipids in human meibomian gland secretions. J Clin Endocrinol Metab 2000; 85: 4866-4873.
47. Krenzer KL, Dana MR, Ullman MD, Cermak JM, Tolls DB, Evans JE, Sullivan DA. Effect of androgen deficiency on the human meibomian gland and ocular surface. J Clin Endocrinol Metab 2000; 85: 4874-4882.
48. Nussey SS, Whitehead SA. Endocrinology: An Integrated Approach. Abingdon, Oxford: Taylor & Francis, 2001.
49. Sullivan DA, Hann LE, Yee L, Allansmith MR. Age- and gender-related influence on the lacrimal gland and tears. Acta Ophthalmol 1990; 68: 188-194.
50. Sullivan DA, Wickham LA, Rocha EM, Kelleher RS, da Silveira LA, Toda I. Influence of gender, sex steroid hormones, and the hypothalamic-pituitary axis on the structure and function of the lacrimal gland. Adv Exp Med Biol 1998; 438: 11-42.
51. Yamagami H, Richards SM, Sullivan BD, Liu M, Steagall RJ, Sullivan DA. Gender-associated differences in gene expression of the meibomian gland. Adv Exp Med Biol 2002; 506: 459-463.
52. Labrie F, Belanger A, Simard J, Van L-T, Labrie C. DHEA and peripheral androgen and estrogen formation: Intracinology. Ann N Y Acad Sci 1995; 774: 16-28.
53. Wierman ME. Sex steroid effects at target tissues: mechanisms of action. Adv Physiol Educ 2007; 31: 26-33.
54. Labrie F, Luu-The V, Lin SX, Labrie C, Simard J, Breton R, Belanger A. The key role of 17 beta-hydroxysteroid dehydrogenases in sex steroid biology. Steroids 1997; 62: 148-158.
55. Schirra F, Suzuki T, Dickinson DP, Townsend DJ, Gipson IK, Sullivan DA. Identification of steroidogenic enzyme mRNAs in the human lacrimal gland, meibomian gland, cornea and conjunctiva. Cornea 2006; 25: 438-442.
56. Labrie F, Luu -The V, Labrie C, Belanger A, Simard J, Lin S-X, Pelletier G. Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone. Endocr Rev 2003; 24: 152-182.
57. Rocha EM, Wickham LA, da Silveira LA, Krenzer KL, Yu FS, Toda I, Sullivan BD et al. Identification of androgen receptor protein and 5alpha-reductase mRNA in human ocular tissues. Br J Ophthalmol 2000; 84: 76-84.
58. Perra MT, Lantini MS, Serra A, Cossu M, De Martini G, Sirigu P. Human meibomian glands: a histochemical study for androgen metabolic enzymes. Invest Ophthalmol Vis Sci 1990; 31: 771-775.
59. Wickham LA, Rocha EM, Gao J, Krenzer KL, da Silveira LA, Toda I, Sullivan DA. Identification and hormonal control of sex steroid receptors in the eye. Adv Exp Med Biol 1998; 438: 95-100.
60. Wickham LA, Gao J, Toda I, Rocha EM, Ono M, Sullivan DA. Identification of androgen, estrogen and progesterone receptor mRNAs in the eye. Acta Ophthalmol Scand 2000; 78: 146-153.
61. Suzuki T, Kinoshita Y, Tachibana M, Matsushima Y, Kobayashi Y, Adachi W, Sotozono C et al. Expression of sex steroid hormone receptors in human cornea. Curr Eye Res 2001; 22: 28-33.
62. Schirra F, Suzuki T, Richards SM, Jensen RV, Liu M, Lombardi MJ, Rowley P et al. Androgen control of gene expression in the mouse meibomian gland. Invest Ophthalmol Vis Sci 2005; 46: 3666-3675.
63. Yamagami H, Schirra F, Liu M, Richards SM, Sullivan BD, Sullivan DA. Androgen influence on gene expression in the meibomian gland. Adv Exp Med Biol 2002; 506: 477-481.
64. Steagall RJ, Yamagami H, Wickham LA, Sullivan DA. Androgen control of gene expression in the rabbit meibomian gland. Adv Exp Med Biol 2002; 506: 465-476.
65. Marin-Castaño ME, Elliot SJ, Potier M, Karl M, Striker LJ, Striker GE, Csaky KG, Cousins SW. Regulation of Estrogen Receptors and MMP-2 Expression by Estrogens in Human Retinal Pigment Epithelium. Invest Ophthalmol Vis Sci 2003; 44: 50-59.
66. McCulley JP, Shine WE. The lipid layer of tears: dependent on meibomian gland function. Exp Eye Res 2004; 78: 361-365.
67. Sullivan DA, Rocha EM, Ullman MD, Krenzer KL, Gao J, Toda I, Dana MR et al. Androgen regulation of the meibomian gland. Adv Exp Med Biol 1998; 438: 327-331.
68. Sullivan DA, Sullivan BD, Ullman MD, Rocha EM, Krenzer KL, Cermak JM, Toda I et al. Androgen influence on the meibomian gland. Invest Ophthalmol Vis Sci 2000; 41: 3732-3742.
69. Sullivan DA, Yamagami H, Liu M, Suzuki T, Krenzer KL, Cermak JM, Sullivan RM et al. Sex steroids, the meibomian gland and evaporative dry eye. Cornea 2000; 19: S128.
70. Sullivan DA, Sullivan BD, Evans JE, Schirra F, Yamagami H, Liu M, Richards SM et al. Androgen deficiency, meibomian gland dysfunction, and evaporative dry eye. Ann N Y Acad Sci 2002; 966: 211-222.
71. Sullivan BD, Evans JE, Dana MR, Sullivan DA. Influence of aging on the polar and neutral lipid profiles in human meibomian gland secretions. Arch Ophthalmol 2006; 124: 1286-1292.
72. Sullivan BD, Evans JE, Dana MR, Sullivan DA. Impact of androgen deficiency on the lipid profiles in human meibomian gland secretions. Adv Exp Med Biol 2002; 506: 449-458.
73. Labrie F, Belanger A, Cusan L, Gomez JL, Candas B. Marked decline in serum concentrations of adrenal C19 sex steroid precursors and conjugated androgen metabolites during aging. J Clin Endocrinol Metab 1997; 82: 2396-2402.
74. Guillon M, Maïssa C. Tear film evaporation-effect of age and gender. Cont Lens Anterior Eye 2010; 33: 171-175.
75. Labrie F. DHEA, important source of sex steroids in men and even more in women. Prog Brain Resh 2010; 182: 97-148.
76. Pochi PE, Strauss JS. Endocrinologic control of the development and activity of the human sebaceous gland. J Invest Dermatol 1974; 62: 191-201.
77. Deplewski D, Rosenfield RL. Role of hormones in pilosebaceous unit development. Endocr Rev 2000; 21: 363-392.
78. Thody AJ, Shuster S. Control and function of sebaceous glands. Physiol Rev 1989; 69: 383-416.
79. Rosignoli C, Nicolas JC, Jomard A, Michel S. Involvement of the SREBP pathway in the mode of action of androgens in sebaceous glands in vivo. Exp Dermatol 2003; 12: 480-489.
80. Hykin PG, Bron AJ. Age-related morphological changes in lid margin and meibomian gland anatomy. Cornea 1992; 11: 334-342.
81. Pochi PE, Strauss JS, Downing DT. Age-related changes in sebaceous gland activity. J Invest Dermatol 1979; 73: 108-111.
82. Driver PJ, Lemp MA. Meibomian gland dysfunction. Surv Ophthalmol 1996; 40: 343-367.
83. Mathers WD, Lane JA, Zimmerman MB. Tear film changes associated with normal aging. Cornea 1996; 15: 229-234.
84. Shimazaki J, Sakata M, Tsubota K. Ocular surface changes and discomfort in patients with meibomian gland dysfunction. Arch Ophthalmol 1995; 113: 1266-1270.
85. Norn M. Expressibility of meibomian secretion. Relation to age, lipid precorneal film, scales, foam, hair and pigmentation. Acta Ophthalmol 1987; 65: 137-142.
86. Mathers WD, Shields WJ, Sachdev MS, Petroll WM, Jester JV. Meibomian gland dysfunction in chronic blepharitis. Cornea 1991; 10: 277-285.
87. Den S, Shimizu K, Ikeda T, Tsubota K, Shimmura S, Shimazaki J. Association between meibomian gland changes and aging, sex, or tear function. Cornea 2006; 25: 651-655.
88. Zeligs M, Gordon K. Dehydroepiandrosterone therapy for the treatment of dry eye disorders. Int Patent Application WO 1994; 94/04155.
89. Worda C, Nepp J, Huber JC, Sator MO. Treatment of keratoconjunctivitis sicca with topical androgen. Maturitas 2001; 37: 209-212.
90. Schirra F, Richards SM, Liu M, Suzuki T, Yamagami H, Sullivan DA. Androgen regulation of lipogenic pathways in the mouse meibomian gland. Exp Eye Res 2006; 83: 291-296.
91. Schirra F, Richards SM, Sullivan DA. Androgen influence on cholesterogenic enzyme mRNA levels in the mouse meibomian gland. Curr Eye Res 2007; 32: 393-398.
92. Obata H. Anatomy and histopathology of human meibomian gland. Cornea 2002; 21: S70-S74.
93. Richards SM, Yamagami H, Schirra F, Suzuki T, Jensen RV, Sullivan DA. Sex-related effect on gene expression in the mouse meibomian gland. Curr Eye Res 2006; 31: 119-128.
94. Esmaeli B, Harvey JT, Hewlett B. Immunohistochemical evidence for estrogen receptors in meibomian glands. Ophthalmology 2000; 107: 180-184.
95. Auw-Haedrich C, Feltgen N. Estrogen receptor expression in meibomian glands and its correlation with age and dry-eye parameters. Graefes Arch Clin Exp Ophthalmol 2003; 241: 705-709.
96. Knop E, Knop N, Millar T, Obata H, Sullivan DA. The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland. Invest Ophthalmol Vis Sci 2011; 52: 1938-1978.
97. Sansone-Bazzano G, Reisner RM, Bazzano G. A possible mechanism of action of estrogen at the cellular level in a model sebaceous gland. J Invest Dermatol 1972; 59: 299-304.
98. Suzuki T, Sullivan BD, Liu M, Schirra F, Richards SM, Yamagami H, Sullivan DA. Estrogen and progesterone effects on the morphology of the mouse meibomian gland. Adv Exp Med Biol 2002; 506: 483-488.
99. Darabad RR, Suzuki T, Richards SM, Jensen RV, Jakobiec FA, Zakka FR, Liu S et al. Influence of aromatase absence on the gene expression and histology of the mouse meibomian gland. Invest Ophthalmol Vis Sci 2013; 54: 987-998.
100. Suzuki T, Schaumberg DA, Sullivan BD, Liu M, Richards SM, Sullivan RM, Dana MR et al. Do estrogen and progesterone play a role in the dry eye of Sjögren's syndrome? Ann N Y Acad Sci 2002; 966: 223-225.
101. Rodriguez AM, Monjo M, Roca P, Palou A. Opposite actions of testosterone and progesterone on UCP1 mRNA expression in cultured brown adipocytes. Cell Mol Life Sci 2002; 59: 1714-1723.
102. Dartt DA. Signal transduction and control of lacrimal gland protein secretion: a review. Curr Eye Res 1989; 8: 619-636.
103. Ubels JL, Gipson IK, Spurr-Michaud SJ, Tisdale AS, Van Dyken RE, Hatton MP. Gene expression in human accessory lacrimal glands of Wolfring. Invest Ophthalmol Vis Sci 2012; 53: 6738-6747.
104. Sullivan DA, Edwards JA, Wickham LA, Pena JD, Gao J, Ono M, Kelleher RS. Identification and endocrine control of sex steroid binding sites in the lacrimal gland. Curr Eye Res 1996; 15: 279-291.
105. Richards SM, Liu M, Jensen RV, Schirra F, Yamagami H, Lombardi MJ, Rowley P et al. Androgen regulation of gene expression in the mouse lacrimal gland. J Steroid Biochem Mol Biol 2005; 96: 401-413.
106. Suzuki T, Schirra F, Richards SM, Treister NS, Lombardi MJ, Rowley P, Jensen RV et al. Estrogen's and progesterone's impact on gene expression in the mouse lacrimal gland. Invest Ophthalmol Vis Sci 2006; 47: 158-168.
107. Sullivan DA, Block L, Pena JDO. Influence of androgens and pituitary hormones on the structural profile and secretory activity of the lacrimal gland. Acta Ophthalmol Scand 1996; 74: 421-435.
108. Azzarolo AM, Mircheff AK, Kaswan RL, Stanczyk FZ, Gentschein E, Becker L, Nassir B, Warren DW. Androgen support of lacrimal gland function. Endocrine 1997; 6: 39-45.
109. Azzarolo AM, Eihausen H, Schechter J. Estrogen prevention of lacrimal gland cell death and lymphocytic infiltration. Exp Eye Res 2003; 77: 347-354.
110. Ishimaru N, Saegusa K, Yanagi K, Haneji N, Saito I, Hayashi Y. Estrogen deficiency accelerates autoimmune exocrinopathy in murine Sjögren's syndrome through fas-mediated apoptosis. Am J Pathol 1999; 155: 173-181.
111. Sullivan DA, Bloch KJ, Allansmith MR. Hormonal influence on the secretory immune system of the eye: androgen control of secretory component production by the rat exorbital gland. Immunology 1984; 52: 239-246.
112. Rocha FJ, Wickham LA, Pena JDO, Gao J, Ono M, Lambert RW, Kelleher RS et al. Influence of gender and the endocrine environment on the distribution of androgen receptors in the lacrimal gland. J Steroid Biochem Mol Biol 1993; 46: 737-749.
113. Chen SP, Massaro-Giordano GMD, Pistilli MMM, Schreiber CA, Bunya VY. Tear osmolarity and dry eye symptoms in women using oral contraception and contact lenses. Cornea 2013; 32: 423-428.
114. Sullivan DA, Krenzer KL, Sullivan BD, Tolls DB, Toda I, Dana MR. Does androgen insufficiency cause lacrimal gland inflammation and aqueous tear deficiency? Invest Ophthalmol Vis Sci 1999; 40: 1261-1265.
115. Sullivan DA, Allansmith MR. Hormonal influence on the secretory immune system of the eye: androgen modulation of IgA levels in tears of rats. J Immunol 1985; 134: 2978-2982.
116. Sullivan DA. Influence of the hypothalamic-pituitary axis on the androgen regulation of the ocular secretory immune system. J Steroid Biochem 1988; 30: 429-433.
117. Sullivan DA, Bloch KJ, Allansmith MR. Hormonal influence on the secretory immune system of the eye: androgen regulation of secretory component levels in rat tears. J Immunol 1984; 132: 1130-1135.
118. Azzarolo AM, Mazaheri AH, Mircheff AK, Warren DW. Sex-dependent parameters related to electrolyte, water and glycoprotein secretion in rabbit lacrimal glands. Curr Eye Res 1993; 12: 795-802.
119. Sullivan DA, Allansmith MR. Hormonal modulation of tear volume in the rat. Exp Eye Res 1986; 42: 131-139.
120. Azzarolo AM, Bjerrum K, Maves CA, Becker L, Wood RL, Mircheff AK, Warren DW. Hypophysectomy-induced regression of female rat lacrimal glands: partial restoration and maintenance by dihydrotestosterone and prolactin. Invest Ophthalmol Vis Sci 1995; 36: 216-226.
121. Azzarolo AM, Wood RL, Mircheff AK, Richters A, Olsen E, Berkowitz M, Bachmann M et al. Androgen influence on lacrimal gland apoptosis, necrosis and lymphocytic infiltration. Invest Ophthalmol Vis Sci 1999; 40: 592-602.
122. Azzarolo AM, Kaswan RL, Mircheff AK, Warren DW. Androgen prevention of lacrimal gland regression after ovariectomy of rabbits. Invest Ophthalmol Vis Sci 1994; 35: 1793.
123. Sullivan DA, Allansmith MR. Hormonal influence on the secretory immune system of the eye: endocrine interactions in the control of IgA and secretory component levels in tears of rats. Immunology 1987; 60: 337-343.
124. Sullivan DA, Hann LE. Hormonal influence on the secretory immune system of the eye: endocrine impact on the lacrimal gland accumulation and secretion of IgA and IgG. J Steroid Biochem 1989; 34: 253-262.
125. Toda I, Wickham LA, Sullivan DA. Gender and androgen treatment influence the expression of proto-oncogenes and apoptotic factors in lacrimal and salivary tissues of MRL/lpr mice. Clin Immunol Immunopathol 1998; 86: 59-71.
126. Gao J, Lambert RW, Wickham LA, Banting G, Sullivan DA. Androgen control of secretory component mRNA levels in the rat lacrimal gland. J Steroid Biochem Mol Biol 1995; 52: 239-249.
127. Winderickx J, Vercaeren I, Verhoeven G, Heyns W. Androgen-dependent expression of cystatin-related protein (CRP) in the exorbital lacrimal gland of the rat. J Steroid Biochem Mol Biol 1994; 48: 165-170.
128. Toda I, Sullivan BD, Wickham LA, Sullivan DA. Gender- and androgen-related influence on the expression of proto-oncogene and apoptotic factor mRNAs in lacrimal glands of autoimmune and non-autoimmune mice. J Steroid Biochem Mol Biol 1999; 71: 49-61.
129. Ono M, Rocha FJ, Sullivan DA. Immunocytochemical location and hormonal control of androgen receptors in lacrimal tissues of the female MRL/Mp-lpr/lpr mouse model of Sjögren's syndrome. Exp Eye Res 1995; 61: 659-666.
130. Lambert RW, Kelleher RS, Wickham LA, Vaerman JP, Sullivan DA. Neuroendocrinimmune modulation of secretory component production by rat lacrimal, salivary, and intestinal epithelial cells. Invest Ophthalmol Vis Sci 1994; 35: 1192-1201.
131. Ubels JL, Wertz JT, Ingersoll KE, Jackson RS 2nd, Aupperlee MD. Down-regulation of androgen receptor expression and inhibition of lacrimal gland cell proliferation by retinoic acid. Exp Eye Res 2002; 75: 561-571.
132. Mostafa S, Seamon V, Azzarolo AM. Influence of sex hormones and genetic predisposition in Sjögren's syndrome: A new clue to the immunopathogenesis of dry eye disease. Exp Eye Res 2012; 96: 88-97.
133. Cornell-Bell AH, Sullivan DA, Allansmith MR. Gender-related differences in the morphology of the lacrimal gland. Invest Ophthalmol Vis Sci 1985; 26: 1170-1175.
134. Sullivan D, Kelleher R, Vaerman J, Hann L. Androgen regulation of secretory component synthesis by lacrimal gland acinar cells in vitro. J Immunol 1990; 145: 4238-4244.
135. Vanaken H, Claessens F, Vercaeren I, Heyns W, Peeters B, Rombauts W. Androgenic induction of cystatin-related protein and the C3 component of prostatic binding protein in primary cultures from the rat lacrimal gland. Mol Cell Endocrinol 1996; 121: 197-205.
136. Obata H, Yamamoto S, Horiuchi H, Machinami R. Histopathologic study of human lacrimal gland. Statistical analysis with special reference to aging. Ophthalmology 1995; 102: 678-686.
137. Alexander WS, Hilton DJ. The role of suppressors of cytokine signaling (SOCS) proteins in regulation of the immune response. Annu Rev Immunol 2004; 22: 503-529.
138. Zylberberg C, Seamon V, Ponomareva O, Vellala K, Deighan M, Azzarolo AM. Estrogen up-regulation of metalloproteinase-2 and -9 expression in rabbit lacrimal glands. Exp Eye Res 2007; 84: 960-972.
139. Gipson IK. Distribution of mucins at the ocular surface. Exp Eye Res 2004; 78: 379-388.
140. Gipson IK, Argüeso P. Role of mucins in the function of the corneal and conjunctival epithelia. In: Kwang WJ ed. International Review of Cytology. Salt Lake City: Academic Press, 2003. p 1-49.
141. Millar TJ, Tragoulias ST, Anderton PJ, Ball MS, Miano F, Dennis GR, Mudgil P. The surface activity of purified ocular mucin at the air-liquid interface and interactions with meibomian lipids. Cornea 2006; 25: 91-100.
142. Rivas L, Oroza MA, Perez-Esteban A, Murube-del-Castillo J. Morphological changes in ocular surface in dry eyes and other disorders by impression cytology. Graefes Arch Clin Exp Ophthalmol 1992; 230: 329-334.
143. Ralph RA. Conjunctival goblet cell density in normal subjects and in dry eye syndromes. Invest Ophthalmol Vis Sci 1975; 14: 299-302.
144. Nelson JD, Wright JC. Conjunctival goblet cell densities in ocular surface disease. Arch Ophthalmol 1984; 102: 1049-1051.
145. Argueso P, Balaram M, Spurr-Michaud S, Keutmann HT, Dana MR, Gipson IK. Decreased levels of the goblet cell mucin MUC5AC in tears of patients with Sjögren syndrome. Invest Ophthalmol Vis Sci 2002; 43: 1004-1011.
146. Danjo Y, Watanabe H, Tisdale AS, George M, Tsumura T, Abelson MB, Gipson IK. Alteration of mucin in human conjunctival epithelia in dry eye. Invest Ophthalmol Vis Sci 1998; 39: 2602-2609.
147. Nelson JD, Havener VR, Cameron JD. Cellulose acetate impressions of the ocular surface. Dry eye states. Arch Ophthalmol 1983; 101: 1869-1872.
148. Bonini S, Mantelli F, Moretti C, Lambiase A, Bonini S, Micera A. Itchy-dry eye associated with polycystic ovary syndrome. Am J Ophthalmol 2007; 143: 763-771.
149. Serrander AM, Peek KE. Changes in contact lens comfort related to the menstrual cycle and menopause. A review of articles. J Am Optom Assoc 1993; 64: 162-166.
150. Feldman F, Bain J, Matuk AR. Daily assessment of ocular and hormonal variables throughout the menstrual cycle. Arch Ophthalmol 1978; 96: 1835-1838.
151. Gipson IK, Inatomi T. Mucin genes expressed by the ocular surface epithelium. Prog Retin Eye Res 1997; 16: 81-98.
152. Inatomi T, Spurr-Michaud S, Tisdale AS, Zhan Q, Feldman ST, Gipson IK. Expression of secretory mucin genes by human conjunctival epithelia. Invest Ophthalmol Vis Sci 1996; 37: 1684-1692.
153. Lange C, Fernandez J, Shim D, Spurr-Michaud S, Tisdale A, Gipson IK. Mucin gene expression is not regulated by estrogen and/or progesterone in the ocular surface epithelia of mice. Exp Eye Res 2003; 77: 59-68.
154. Inatomi T, Spurr-Michaud S, Tisdale AS, Gipson IK. Human corneal and conjunctival epithelia express MUC1 mucin. Invest Ophthalmol Vis Sci 1995; 36: 1818-1827.
155. Gipson IK, Hori Y, Argüeso P. Character of ocular surface mucins and their alteration in dry eye disease. Ocul Surf 2004; 2: 131-148.
156. Mantelli F, Moretti C, Micera A, Bonini S. Conjunctival mucin deficiency in complete androgen insensitivity syndrome (CAIS). Graefes Arch Clin Exp Ophthalmol 2007; 245: 899-902.
157. Mitchell S, Abel P, Madaan S, Jeffs J, Chaudhary K, Stamp G, Lalani E-N. Androgen-dependent regulation of human MUC1 mucin expression. Neoplasia 2002; 4: 9-18.
158. Millodot M. The influence of pregnancy on the sensitivity of the cornea. Br J Ophthalmol 1977; 61: 646-649.
159. Affinito P, Di Spiezio Sardo A, Di Carlo C, Sammartino A, Tommaselli GA, Bifulco G, Loffredo A et al. Effects of hormone eplacement therapy on ocular function in postmenopause. Menopause 2003; 10: 482-487.
160. Kiely PM, Carney LG, Smith G. Menstrual cycle variations of corneal topography and thickness. Am J Optom Physiol Opt 1983; 60: 822-829.
161. Riss B, Binder S, Riss P, Kemeter P. Corneal sensitivity during the menstrual cycle. Br J Ophthalmol 1982; 66: 123-126.
162. Guttridge NM. Changes in ocular and visual variables during the menstrual cycle. Ophthalmic Physiol Opt 1994; 14: 38-48.
163. Soni PS. Effects of oral contraceptive steroids on the thickness of human cornea. Am J Optom Physiol Opt 1980; 57: 825-834.
164. Millodot M, Lamont A. Influence of menstruation on corneal sensitivity. Br J Ophthalmol 1974; 58: 752-756.
165. Ward MM, Stone SC, Sandman CA. Visual perception in women during the menstrual cycle. Physiol Behav 1978; 20: 239-243.
166. Pelit A, Bagis T, Kayaselcuk F, Dursun D, Akova Y, Aydin P. Tear function tests and conjunctival impression cytology before and after hormone replacement therapy in postmenopausal women. Eur J Ophthalmol 2003; 13: 337-342.
167. Vavilis D, Agorastos T, Vakiani M, Jafetas J, Panidis D, Konstantinidis T, Bontis J. The effect of transdermal estradiol on the conjunctiva in postmenopausal women. Eur J Obstet Gynecol Reprod Biol 1997; 72: 93-96.
168. Tomlinson A, Pearce EI, Simmons PA, Blades K. Effect of oral contraceptives on tear physiology. Ophthalmic Physiol Opt 2001; 21: 9-16.
169. Blalock TD, Spurr-Michaud SJ, Tisdale AS, Gipson IK. Release of membrane-associated mucins from ocular surface epithelia. Invest Ophthalmol Vis Sci 2008; 49: 1864-1871.
170. Caffery B, Heynen ML, Joyce E, Jones L, Ritter R 3rd, Senchyna M. MUC1 expression in Sjögren's syndrome, KCS, and control subjects. Mol Vis 2010; 16: 1720-1727.
171. Caffery B, Joyce E, Heynen ML, Jones L, Ritter R 3rd, Gamache DA, Senchyna M. MUC16 expression in Sjögren's syndrome, KCS, and control subjects. Mol Vis 2008; 14: 2547-2555.
172. Albertsmeyer A-C, Kakkassery V, Spurr-Michaud S, Beeks O, Gipson IK. Effect of pro-inflammatory mediators on membrane-associated mucins expressed by human ocular surface epithelial cells. Exp Eye Res 2010; 90: 444-451.
173. Aragona P, Puzzolo D, Micali A, Ferreri G, Britti D. Morphological and morphometric analysis on the rabbit conjunctival goblet cells in different hormonal conditions. Exp Eye Res 1998; 66: 81-88.
174. Ansar Ahmed S, Penhale WJ, Talal N. Sex hormones, immune responses, and autoimmune diseases. Mechanisms of sex hormone action. Am J Pathol 1985; 121: 531-551.
175. Homo-Delarche F, Fitzpatrick F, Christeff N, Nunez EA, Bach JF, Dardenne M. Sex steroids, glucocorticoids, stress and autoimmunity. J Steroid Biochem Mol Biol 1991; 40: 619-637.
176. Olsen NJ, Kovacs WJ. Gonadal steroids and immunity. Endocr Rev 1996; 17: 369-384.
177. Pflugfelder SC, Jones D, Ji Z, Afonso A, Monroy D. Altered cytokine balance in the tear fluid and conjunctiva of patients with Sjögren's syndrome keratoconjunctivitis sicca. Curr Eye Res 1999; 19: 201-211.
178. Solomon A, Dursun D, Liu Z, Xie Y, Macri A, Pflugfelder SC. Pro- and anti-inflammatory forms of interleukin-1 in the tear fluid and conjunctiva of patients with dry eye disease. Invest Ophthalmol Vis Sci 2001; 42: 2283-2292.
179. Brignole F, Pisella PJ, Goldschild M, De Saint Jean M, Goguel A, Baudouin C. Flow cytometric analysis of inflammatory markers in conjunctival epithelial cells of patients with dry eyes. Invest Ophthalmol Vis Sci 2000; 41: 1356-1363.
180. Li DQ, Lokeshwar BL, Solomon A, Monroy D, Ji Z, Pflugfelder SC. Regulation of MMP-9 production by human corneal epithelial cells. Exp Eye Res 2001; 73: 449-459.
181. Chotikavanich S, de Paiva CS, Li DQ, Chen JJ, Bian F, Farley WJ, Pflugfelder SC. Production and activity of matrix metalloproteinase-9 on the ocular surface increase in dysfunctional tear syndrome. Invest Ophthalmol Vis Sci 2009; 50: 3203-3209.
182. Pflugfelder SC, Farley W, Luo L, Chen LZ, de Paiva CS, Olmos LC, Li D-Q et al. Matrix metalloproteinase-9 knockout confers resistance to corneal epithelial barrier disruption in experimental dry eye. Am J Pathol 2005; 166: 61-71.
183. Jansson L, Holmdahl R. Estrogen-mediated immunosuppression in autoimmune diseases. Inflamm Res 1998; 47: 290-301.
184. Cutolo M, Sulli A, Capellino S, Villaggio B, Montagna P, Seriolo B, Straub RH. Sex hormones influence on the immune system: basic and clinical aspects in autoimmunity. Lupus 2004; 13: 635-638.
185. Bizzarro A, Valentini G, Di Martino G, DaPonte A, De Bellis A, Iacono G. Influence of testosterone therapy on clinical and immunological features of autoimmune diseases associated with Klinefelter's syndrome. J Clin Endocrinol Metab 1987; 64: 32-36.
186. He WW, Kumar MV, Tindall DJ. A frame-shift mutation in the androgen receptor gene causes complete androgen insensitivity in the testicular-feminized mouse. Nucleic Acids Res 1991; 19: 2373-2378.
187. Suzuki T, Sullivan D. Estrogen stimulation of cytokine gene expression in human corneal epithelial cells. Invest Ophthalmol Vis Sci 2002; 43: E-Abstract 90.
188. Wang C, Shi X, Chen X, Wu H, Zhang H, Xie J, Yang X et al. 17-estradiol inhibits hyperosmolarity-induced proinflammatory cytokine elevation via the p38 MAPK pathway in human corneal epithelial cells. Mol Vis 2012; 18: 1115-1122.
189. Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta 2011; 1813: 878-888.
190. Scott G, Yiu SC, Wasilewski D, Song J, Smith RE. Combined esterified estrogen and methyltestosterone treatment for dry eye syndrome in postmenopausal women. Am J Ophthalmol 2005; 139: 1109-1110.
191. Forsblad-d'Elia H, Carlsten H, Labrie F, Konttinen YT, Ohlsson C. Low serum levels of sex steroids are associated with disease characteristics in primary Sjögren's syndrome; supplementation with dehydroepiandrosterone restores the concentrations. J Clin Endocrinol Metab 2009; 94: 2044-2051.
192. Pillemer SR, Brennan MT, Sankar V, Leakan RA, Smith JA, Grisius M, Ligier S et al. Pilot clinical trial of dehydroepiandrosterone (DHEA) versus placebo for Sjögren's syndrome. Arthritis Rheum 2004; 51: 601-604.
193. Kemdinum Idu F, Osita Emina M, Oyem Ubaru C. Tear secretion and tear stability of women on hormonal contraceptives. J Optom 2013; 06: 45-50.
194. Shaharuddin B, Ismail-Mokhtar S, Hussein E. Dry eye in post-menopausal Asian women on hormone replacement therapy. Int J Ophthalmol 2008; 1: 158-160.
195. Coksuer H, Ozcura F, Oghan F, Haliloglu B, Coksuer C. Effects of estradiol-drospirenone on ocular and nasal functions in postmenopausal women. Climacteric 2011; 14: 482-487.
196. Evans V, Miller TJ, Eden JA, Willcox MDP. Menopause, hormone replacement therapy and tear function. Adv Exp Med Biol 2002; 507: 1029-1033.
197. Moon JH, Jung JW, Shin KH, Paik HJ. Effect of hormone replacement therapy on dry eye syndrome in postmenopausal women: a prospective study. J Korean Ophthalmol Soc 2010; 51: 175-179.
198. Jensen AA, Higginbotham EJ, Guzinski GM, Davis IL, Ellish NJ. A survey of ocular complaints in postmenopausal women. J Assoc Acad Minor Phys 2000; 11: 43-49.
199. Altintaş Ö, Caglar Y, Yüksel N, Demirci A, Karabaş L. The effects of menopause and hormone replacement therapy on quality and quantity of tear, intraocular pressure and ocular blood flow. Ophthalmologica 2004; 218: 120-129.
200. Guaschino S, Grimaldi E, Sartore A, Mugittu R, Mangino F, Bortoli P, Pensiero S et al. Visual function in menopause: the role of hormone replacement therapy. Menopause 2003; 10: 53-57.
201. Okoń A, Jurowski P, Goś R. The influence of the hormonal replacement therapy on the amount and stability of the tear film among peri- and postmenopausal women. Klin Oczna 2001; 103: 177-181.
202. Sator MO, Joura EA, Golaszewski T, Gruber D, Frigo P, Metka M, Hommer A et al. Treatment of menopausal keratoconjunctivitis sicca with topical oestradiol. Br J Obstet Gynaecol 1998; 105: 100-102.
203. Akramian J, Wedrich A, Nepp J, Sator M. Estrogen therapy in keratoconjunctivitis sicca. Adv Exp Med Biol 1998; 438: 1005-1009.
204. Kuscu NK, Toprak AB, Vatansever S, Koyuncu FM, Guler C. Tear function changes of postmenopausal women in response to hormone replacement therapy. Maturitas 2003; 44: 63-68.
205. Piwkumsribonruang N, Somboonporn W, Luanratanakorn P, Kaewrudee S, Tharnprisan P, Soontrapa S. Effectiveness of hormone therapy for treating dry eye syndrome in postmenopausal women: a randomized trial. J Med Assoc Thai 2010; 93: 647-652.
206. Taner P, Akarsu C, Atasoy P, Bayram M, Ergin A. The effects of hormone replacement therapy on ocular surface and tear function tests in postmenopausal women. Ophthalmologica 2004; 218: 257-259.
207. Verit F, Oguz H, Ozkul Y, Bozkurt O. Long-term effects of tibolone on ocular functions in postmenopausal women. Arch Gynecol Obstet 2007; 275: 255-261.
208. Lekskul A, Nimvorapun T, Manonai J, Hanutsaha P, Tasanee Sirikul S. The study of tear function, central corneal thickness and corneal endothelial cell count in postmenopausal hormone replacement therapy. Thai J Ophthalmol 2004; 18: 121-127.