The Human Lacrimal Gland: Historical Perspectives, Current Understanding, and Recent Advances

References

• Vingerhoets A. Why only humans weep: unravelling the mysteries of tears. 1st. Oxford: Oxford University Press; 2013.
   Google Scholar
• Donthineni PR, Kammari P, Shanbhag SS, Singh V, Das AV, Basu S. Incidence, demographics, types and risk factors of dry eye disease in India: electronic medical records driven big data analytics report I. Ocul Surf. 2019;17(2):250–56. doi:10.1016/j.jtos.2019.02.007.
   PubMed Web of Science ®Google Scholar
• Hirschberg J. The renaissance of ophthalmology in 18th century. In: Hirschberg J editor. The history of ophthalmology. Vol. 1. Amsterdam: Wayenborg publications; 1984.
   Google Scholar
• Ebers G, Ebers P, HermetischeBuch D URL link: https://digi.ub.uni-heidelberg.de/diglit/ebers1875bd1/0001
   Google Scholar
• Susrutha I. Susrutha Samhita Uttaratantra 1/21.
   Google Scholar
• Susrutha I. Susrutha Samhita Uttaratantra, 6/6-7, 22–23.
   Google Scholar
• Dalhana. Susrutha Samhita Chowkhambha Orientalia Varanasi, 2002; Uttaratantra 1/18.
   Google Scholar
• Susrutha I. Susruta samhita Sutrasthana 14/3.
   Google Scholar
• Sushruta. Sushruta samhita dalhana comm.nibandhasangraha, chowkhambha orientalia varanasi, 2002, Uttaratantra 1/16.
   Google Scholar
• Duke-Elder S, Wybar KC. The lacrimal glands. In: Duke-Elder S editor. System of ophthalmology. vol. ii. the anatomy of the visual system. Vols. 526–7. London: Henry Kimpton; 1961. p. 562–68.
   Google Scholar
• Holomanova A, Ivanova A, Brucknerova I. Niels Stensen–prestigious scholar of the 17th century. Bratisl Lek Listy. 2002;103:90–93.
   PubMedGoogle Scholar
• Tubbs RS, Mortazavi MM, Shoja MM, Loukas M, Cohen-Gadol AA. The bishop and anatomist Niels Stensen (1638-1686) and his contributions to our early understanding of the brain. Childs Nerv Syst. 2011;27(1):1–6. doi:10.1007/s00381-010-1236-5.
   PubMed Web of Science ®Google Scholar
• Whitnall SE. Anatomy of the human orbit and accessory organs of vision. 2 ed. London: Oxford Univ Press; 1932. p. 209.
   Google Scholar
• Sappey. CR. Soc Biol Mem (Paris). 1853;5:13.
   Google Scholar
• Krause C. Z Rat Med. 1854;4:337.
   Google Scholar
• Krause F. Die Neuralgie D Trigeminus, Leipzig. 1896.
   Google Scholar
• Wolfring. Zbl Med Wiss. 1872;10:852.
   Google Scholar
• Ciaccio Moleschott’s. Untersuch Naturlehre D Mensch. 1876;11:420.
   Google Scholar
• Murube J. The Schirmer test: celebration of its first centenary. Ocul Surf. 2003;1(4):157–59. doi:10.1016/S1542-0124(12)70011-3.
   PubMedGoogle Scholar
• Schirmer O. Sur la sécrétion et l’excrètion lacrymale aprés extirpation du sac. com. to the deutsch ophthalmol ges (heidelberg 3 aug 1901). Abstract in Ann Ocul (Paris). 1902;128:218–19.
   Google Scholar
• Schirmer O. Principios y métodos de vdeterminación funcional de lasv glándulas lagrimales. Arch Oftalmol Hisp-Amer. 1903;3:366–67.
   Google Scholar
• Schirmer O. Über lidschlaglähmung und lidschlusslähmung zugleich ein beitrag zur lehre von der tränenabfuhr. Zeitsch Augenheilk. 1904;11:97–105.
   Google Scholar
• Schirmer O. Über den einfluss des sympathicus auf die funktion der tr.nendrüse. Pflu¨ger’s Arch Ges Physiol. 1909;126(5–8):351–70. doi:10.1007/BF01677796.
   Google Scholar
• Schirmer O. Studien zur physiologie und pathologie der tränenabsonderung und tränenabfuhr. Graefe’s Arch Ophthalmol. 1903;56(2):197–291. doi:10.1007/BF01946264.
   Google Scholar
• Jones LT. The lacrimal secretory system and its treatment. Am J Ophthalmol. 1966;62(1):47–60. doi:10.1016/0002-9394(66)91676-X.
   PubMed Web of Science ®Google Scholar
• Ghafoor M. Sjögren’s before sjögren: did henrik sjögren (1899-1986) really discover sjögren’s disease? J Maxillofac Oral Surg. 2012;11(3):373–74. doi:10.1007/s12663-011-0303-0.
   PubMedGoogle Scholar
• Obata H. Anatomy and histopathology of the human lacrimal gland. Cornea. 2006;25(10 Suppl 1):S82–9. Review. doi:10.1097/01.ico.0000247220.18295.d3.
   PubMed Web of Science ®Google Scholar
• Jakobiec FA, Iwamoto T. The ocular adnexa: lids, conjunctiva, and orbit. In: Fine BS, Yanoff M, Hagerstown MD, Row H editors. Ocular histology: a text and atlas.. 2 ed. New York: Harper and Row; 1979. p. 318
   Google Scholar
• Obata H, Yamamoto S, Horiuchi H, Machinami R. Histopathologic study of human lacrimal gland. Statistical analysis with special reference to aging. Ophthalmol. 1995;102(4):678–86. doi:10.1016/S0161-6420(95)30971-2.
   PubMed Web of Science ®Google Scholar
• Takahashi Y, Watanabe A, Matsuda H, Nakamura Y, Nakano T, Asamoto K, Ikeda H, Kakizaki H. Anatomy of secretory glands in the eyelid and conjunctiva: a photographic review. Ophthalmic Plast Reconstr Surg. 2013;29(3):215–19. doi:10.1097/IOP.0b013ex3182833dee.
   PubMed Web of Science ®Google Scholar
• Lorber M. Gross characteristics of normal human lacrimal glands. Ocul Surf. 2007;5(1):13–22. Review. doi:10.1016/S1542-0124(12)70049-6.
   PubMed Web of Science ®Google Scholar
• Eisler P. Die anatomie des menschlichen auges. in: schieck f, bruchner a editors. kurzes handbuch ophthalmol. Vol. 1. Berlin: Julius Springer; 1930. p. 237–38.
   Google Scholar
• Prager A. Macroscopic and microscopic investigations on senile atrophy of the lacrimal gland. Bibl Ophthalmol. 1966;69:146–58.
   PubMedGoogle Scholar
• Forrester JV, Dick AD, McMenamin PG, Lee WR. The eye. basic sciences in practice. 2 ed. Edinburgh: WB Saunders; 2002. p. 84.
   Google Scholar
• Werb A. The anatomy of the lacrimal system. In: Milder B, Weil BA, editors. The lacrimal system. Norwalk, CT: Appleton-Century-Crofts; 1983. p. 23–32.
   Google Scholar
• Tripathi RC, Tripathi BJ. Anatomy of the human eye, orbit, and adnexa. In: Davson H editor. The eye. Vol. 1A. 3. Orlando, FL: Academic Press; 1984. p. 79.
   Google Scholar
• Murray AN. Anatomy (gross) of the human eye and of its appendages. In: Wood CA editor. The American encyclopedia and dictionary of ophthalmology. Vol. 1. Chicago, IL: Cleveland Press; 1913. p. p 350.
   Google Scholar
• Noyes HD. A textbook of diseases of the eye. New York, NY: Wm Wood Co; 1894. p 292.
   Google Scholar
• Alt A. Original contributions concerning the glandular structures appertaining to the human eye and its appendages. Trans Acad Sci St Louis. 1900;10:185–207.
   Google Scholar
• Kim EC, Doh SH, Chung SY, Yoon SY, Kim MS, Chung SK, Shin MC, Hwang HS. Direct visualization of aqueous tear secretion from lacrimal gland. Acta Ophthalmol. 2017;95(4):e314–e322. doi:10.1111/aos.13335.
   PubMed Web of Science ®Google Scholar
• Tucker SM, Lambert RW. Vascular anatomy of the lacrimal gland. Ophthalmic Plast Reconstr Surg. 1998;14(4):235–38. doi:10.1097/00002341-199807000-00002.
   PubMed Web of Science ®Google Scholar
• Scott G, Balsiger H, Kluckman M, Fan J, Gest T. Patterns of innervation of the lacrimal gland with clinical application. Clin Anat. 2014;27(8):1174–77. doi:10.1002/ca.22447.
   PubMed Web of Science ®Google Scholar
• Dartt DA. Neural regulation of lacrimal gland secretory processes: relevance in dry eye diseases. Prog Retin Eye Res. 2009;28(3):155–77. doi:10.1016/j.preteyeres.2009.04.003.
   PubMed Web of Science ®Google Scholar
• Seifert P, Stuppi S, Spitznas M, Weihe E. Differential distribution of neuronal markers and neuropeptides in the human lacrimal gland. Graefe’s Arch Clin Exp Ophthalmol. 1996;234(4):232–40. doi:10.1007/BF00430415.
   PubMed Web of Science ®Google Scholar
• Seifert P, Stuppi S, Spitznas M. Distribution pattern of nervous tissue and peptidergic nerve fibers in accessory lacrimal glands. Curr Eye Res. 1997;16(4):298–302. doi:10.1076/ceyr.16.4.298.10698.
   PubMed Web of Science ®Google Scholar
• Seifert P, Spitznas M. Demonstration of nerve fibers in human accessory lacrimal glands. Graefes Arch Clin Exp Ophthalmol. 1994;232(2):107–14. doi:10.1007/BF00171672.
   PubMed Web of Science ®Google Scholar
• Ruskell GL. Nerve terminals and epithelial cell variety in the human lacrimal gland. Cell Tissue Res. 1975;158(1):121. doi:10.1007/BF00219955.
   PubMed Web of Science ®Google Scholar
• Esmaeli-Gutstein B, Hewlett BR, Harvey JT. Characterization of adrenergic receptors in the accessory lacrimal glands of the upper eyelid. Ophthalmic Plast Reconstr Surg. 1999;15(4):245–51. doi:10.1097/00002341-199907000-00005.
   PubMed Web of Science ®Google Scholar
• Gilbard JP, Rossi SR, Heyda KG, Dartt DA. Stimulation of tear secretion by topical agents that increase cyclic nucleotide levels. Invest Ophthalmol Vis Sci. 1990;31:1381–88.
   PubMed Web of Science ®Google Scholar
• Paulsen F, Langer G, Hoffmann W, Berry M. Human lacrimal gland mucins. Cell Tissue Res. 2004;316(2):167–77. doi:10.1007/s00441-004-0877-7.
   PubMed Web of Science ®Google Scholar
• Kobayashi M. Studies on lacrimal glands by use of electron microscope. Acta SOC Ophthal Jap. 1958;62:230–41.
   Google Scholar
• Egeberg J, Jensen QA. The ultrastructure of the acini of the human lacrimal gland. Acta Ophthalmol (Copenh). 1969;47(2):400–10. doi:10.1111/j.1755-3768.1969.tb02897.x.
   PubMed Web of Science ®Google Scholar
• Ito T, Shibasaki S. Lichtmikroskopische untersuchungen iiber die glandula lacrimalis des menschen. Arch Histol Jap. 1964;25(2):117–44. doi:10.1679/aohc1950.25.117.
   PubMedGoogle Scholar
• Vigneswaran N, Wilk CM, Heese A, Hornstein OP, Naumann GO. Immunohistochemical characterization of epithelial cells in human lacrimal glands. I. Normal major and accessory lacrimal glands. Graefes Arch Clin Exp Ophthalmol. 1990;228(1):58–64. doi:10.1007/BF02764293.
   PubMed Web of Science ®Google Scholar
• Franklin RM, Kenyon KR, Tomasi TB. [r.: immunohistologic studies of human lacrimal gland. Localization of immunoglobulins, secretory component and lactoferrin. J Immunol. 1973;110:984.
   Web of Science ®Google Scholar
• Kivelä T. Antigenic profile of the human lacrimal gland. J Histochem Cytochem. 1992;40(5):629–42. doi:10.1177/40.5.1374091.
   PubMed Web of Science ®Google Scholar
• Allansmith MR, Kajiyama G, Abelson MB, Simon MA. Plasma cell content of main and accessory lacrimal glands and conjunctiva. Am J Ophthalmol. 1976;82(6):819. doi:10.1016/0002-9394(76)90056-8.
   PubMed Web of Science ®Google Scholar
• Sullivan DA, Hann LE, Yee L, Allansmith MR. Age and gender-related influence on the lacrimal gland and tears. Acta Ophthalmol (Copenh). 1990;68(2):188–94. doi:10.1111/j.1755-3768.1990.tb01902.x.
   PubMed Web of Science ®Google Scholar
• Cornell-Bell AH, Sullivan DA, Allansmith MR. Gender-related differences in the morphology of the lacrimal gland. Invest Ophthalmol Vis Sci. 1985;26:1170–75.
   PubMed Web of Science ®Google Scholar
• Rocha EM, Alves M, Rios JD, Dartt DA. The aging lacrimal gland: changes in structure and function. Ocul Surf. 2008;6(4):162–74. doi:10.1016/S1542-0124(12)70177-5.
   PubMed Web of Science ®Google Scholar
• Gillette TE, Allansmith MR, Greiner JV, Janusz M. Histologic and immunohistologic comparison of main and accessory lacrimal tissue. Am J Ophthalmol. 1980;89(5):724–30. doi:10.1016/0002-9394(80)90295-0.
   PubMed Web of Science ®Google Scholar
• Seifert P, Spitznas M, Koch F, Cusumano A. The architecture of human accessory lacrimal glands. Ger J Ophthalmol. 1993;2:444–54.
   PubMedGoogle Scholar
• De La Cuadra-Blanco C, Peces-Pena MD, Merida-Velasco JR. Morphogenesis of the human lacrimal gland. J Anat. 2003;203(5):531–36. doi:10.1046/j.1469-7580.2003.00233.x.
   PubMed Web of Science ®Google Scholar
• Tiwari S, Ali MJ, Vemuganti GK. Human lacrimal gland regeneration: perspectives and review of literature. Saudi J Ophthalmol. 2014;28(1):12–18. doi:10.1016/j.sjopt.2013.09.004.
   PubMedGoogle Scholar
• Dietrich J, Schrader S. Towards lacrimal gland regeneration: current concepts and experimental approaches. Curr Eye Res. 2020;45(3):230–40. doi:10.1080/02713683.2019.1637438.
   PubMed Web of Science ®Google Scholar
• Gromova A, Voronov DA, Yoshida M, Thotakura S, Meech R, Dartt DA, Makarenkova HP. Lacrimal gland repair using progenitor cells. Stem Cells Transl Med. 2017;6(1):88–98. doi:10.5966/sctm.2016-0191.
   PubMed Web of Science ®Google Scholar
• Ali M, Shah D, Pasha Z, Jassim SH, Jassim Jaboori A, Setabutr P, Aakalu VK. Evaluation of accessory lacrimal gland in muller’s muscle conjunctival resection specimens for precursor cell markers and biological markers of dry eye disease. Curr Eye Res. 2017;42(4):491–97. doi:10.1080/02713683.2016.1214966.
   PubMed Web of Science ®Google Scholar
• Hirayama M, Liu Y, Kawakita T, Shimmura S, Tsubota K. Cytokeratin expression in mouse lacrimal gland germ epithelium. Exp Eye Res. 2016;146:54–59. doi:10.1016/j.exer.2015.11.020.
   PubMed Web of Science ®Google Scholar
• Meneray MA, Fields TY, Moses RL, Bromberg BB, Moses RL, Fields TY, Moses RL, Bromberg BB, Moses RL, Fields TY, et al. Morphology and physiologic responsiveness of cultured rabbit lacrimal acini. Invest Ophthalmol Vis Sci. 1994;35:4144–58.
   PubMed Web of Science ®Google Scholar
• Rismondo V, Gierow JP, Lambert RW, Golchini K, Feldon SE, Mircheff AK. Rabbit lacrimal acinar cells in primary culture: morphology and acute responses to cholinergic stimulation. Invest Ophthalmol Vis Sci. 1994;35:1176–83.
   PubMed Web of Science ®Google Scholar
• Garg A, Zhang X. Lacrimal gland development: from signaling interactions to regenerative medicine. Dev Dyn. 2017;246(12):970–80. doi:10.1002/dvdy.24551.
   PubMed Web of Science ®Google Scholar
• Shatos MA, Haugaard-Kedstrom L, Hodges RR, Dartt DA. Isolation and characterization of progenitor cells in uninjured, adult rat lacrimal gland. Invest Ophthalmol Vis Sci. 2012;53(6):2749–59. doi:10.1167/iovs.11-9025.
   PubMed Web of Science ®Google Scholar
• Spaniol K, Metzger M, Roth M, Greve B, Mertsch S, Geerling G, Schrader S. Engineering of a secretory active three-dimensional lacrimal gland construct on the basis of decellularized lacrimal gland tissue. Tissue Eng Part A. 2015;21(19–20):2605–17. doi:10.1089/ten.tea.2014.0694.
   PubMed Web of Science ®Google Scholar
• Lin H, Liu Y, He H, Botsford B, Yiu S. Lacrimal gland repair after short-term obstruction of excretory duct in rabbits. Sci Rep. 2017;7(1):8290. doi:10.1038/s41598-017-08197-2.
   PubMed Web of Science ®Google Scholar
• Liu Y, Hirayama M, Kawakita T, Tsubota K. A ligation of the lacrimal excretory duct in mouse induces lacrimal gland inflammation with proliferative cells. Stem Cells Int. 2017;2017:4923426.
   PubMed Web of Science ®Google Scholar
• Zoukhri D, Fix A, Alroy J, Kublin CL. Mechanisms of murine lacrimal gland repair after experimentally induced inflammation. Invest Ophthalmol Vis Sci. 2008;49(10):4399. doi:10.1167/iovs.08-1730.
   PubMed Web of Science ®Google Scholar
• Dietrich J, Schlegel C, Roth M, Witt J, Geerling G, Mertsch S, Schrader S. Comparative analysis on the dynamic of lacrimal gland damage and regeneration after Interleukin-1α or duct ligation induced dry eye disease in mice. Exp Eye Res. 2018;172:66–77. doi:10.1016/j.exer.2018.03.026.
   PubMed Web of Science ®Google Scholar
• Villatoro AJ, Fernández V, Claros S, Rico-Llanos GA, Becerra J, Andrades JA. Use of adipose-derived mesenchymal stem cells in keratoconjunctivitis sicca in a canine model. Biomed Res Int. 2015;2015:1–10. doi:10.1155/2015/527926.
   Web of Science ®Google Scholar
• Lee MJ, Ko AY, Ko JH, Lee HJ, Kim MK, Wee WR, Khwarg SI, Oh JY. Mesenchymal stem/stromal cells protect the ocular surface by suppressing inflammation in an experimental dry eye. Mol Ther. 2015;23(1):139–46. doi:10.1038/mt.2014.159.
   PubMed Web of Science ®Google Scholar
• Bittencourt MK, Barros MA, Martins JFP, Vasconcellos JPC, Morais BP, Pompeia C, Bittencourt MD, KdS E, Kerkis I, Wenceslau CV, et al. Allogeneic mesenchymal stem cell transplantation in dogs with keratoconjunctivitis sicca. Cell Med. 2016;8(3):63–77. doi:10.3727/215517916X693366.
   PubMed Web of Science ®Google Scholar
• Aluri HS, Samizadeh M, Edman MC, Hawley DR, Armaos HL, Janga SR, Meng Z, Sendra VG, Hamrah P, Kublin CL. Delivery of bone marrow-derived mesenchymal stem cells improves tear production in a mouse model of sjögren’s syndrome. Stem Cells Int. 2017;2017:1–10. doi:10.1155/2017/3134543.
   Web of Science ®Google Scholar
• Shi B, Qi J, Yao G, Feng R, Zhang Z, Wang D, Chen C, Tang X, Lu L, Chen W, et al. Mesenchymal stem cell transplantation ameliorates sjögren’s syndrome via suppressing il-12 production by dendritic cells. Stem Cell Res Ther. 2018;9(1):308. doi:10.1186/s13287-018-1023-x.
   PubMed Web of Science ®Google Scholar
• Dietrich J, Roth M, König S, Geerling G, Mertsch S, Schrader S. Analysis of lacrimal gland derived mesenchymal stem cell secretome and its impact on epithelial cell survival. Stem Cell Res. 2019;38:101477. doi:10.1016/j.scr.2019.101477.
   PubMed Web of Science ®Google Scholar
• Weng J, He C, Lai P, Luo C, Guo R, Wu S, Geng S, Xiangpeng A, Liu X, Du X. Mesenchymal stromal cells treatment attenuates dry eye in patients with chronic graft-versus- host disease. Mol Ther. 2012;20(12):2347–54. doi:10.1038/mt.2012.208.
   PubMed Web of Science ®Google Scholar
• Mafee MF, Haik BG. Lacrimal gland and fossa lesions: role of computed tomography. Radiol Clin North Am. 1987;25:767–79.
   PubMed Web of Science ®Google Scholar
• Kawai Y, Sumi M, Kitamori H, Takagi Y, Nakamura T. Diffusion weighted MR microimaging of the lacrimal glands in patients with Sjogren’s syndrome. AJR Am J Roentgenol. 2005;184(4):1320–25. doi:10.2214/ajr.184.4.01841320.
   PubMed Web of Science ®Google Scholar
• Sato EA, Matsumoto Y, Dogru M, Kaido M, Wakamatsu T, Ibrahim OMA, Obata H, Tsubota K. Lacrimal gland in sjögren’s syndrome. Ophthalmol. 2010;117(5):1055–1055.e3. doi:10.1016/j.ophtha.2009.11.034.
   PubMed Web of Science ®Google Scholar
• Doh SH, Kim EC, Chung SY, Kim MS, Chung SK, Shin MC, Hwang HS. Optical coherence tomography imaging of human lacrimal glands: an in vivo study. Ophthalmol. 2015;122(11):2364–66. doi:10.1016/j.ophtha.2015.05.020.
   PubMed Web of Science ®Google Scholar
• Singh S, Basu S. Secretory ductules of the lacrimal gland. Ophthalmic Plast Reconst Surg. 2020; 1. [In press]. doi:10.1097/IOP.0000000000001687.
   PubMed Web of Science ®Google Scholar
• Jordan A, Baum J. Basal tear flow: does it exist? Ophthalmol (Rochester). 1980;87(9):920–30. doi:10.1016/S0161-6420(80)35143-9.
   PubMed Web of Science ®Google Scholar
• Scherz W, Dohlman CH. Is the lacrimal gland dispensable? Keratoconjunctivitis sicca after lacrimal gland removal. Arch Ophthalmol. 1975;93(4):281–83. doi:10.1001/archopht.1975.01010020291009.
   PubMedGoogle Scholar
• Lamberts P, Foster CS, Perry HD. The Schirmer test after topical anesthesia, and the tear meniscus height in normal eyes. Arch Ophthalmol. 1979;97(6):1082–85. doi:10.1001/archopht.1979.01020010536004.
   PubMedGoogle Scholar
• Abusharha AA, AlShehri TM, Hakami AY, Alsaqr AM, Fagehi RA, Alanazi SA, Masmali AM. Analysis of basal and reflex human tear osmolarity in normal subjects: assessment of tear osmolarity. Ther Adv Ophthalmol. 2018;10:2515841418794886.
   Web of Science ®Google Scholar
• Singh S, Basu S. Effect of topical anesthesia on the secretory activity of the main lacrimal gland. Cornea.2020; [In press].
   Web of Science ®Google Scholar
• Stapleton F, Alves M, Bunya VY, Jalbert I, Lekhanont K, Malet F, Na KS, Schaumberg D, Uchino M, Vehof J, et al. TFOS DEWS II Epidemiology Report. Ocul Surf. 2017;15(3):334–65. doi:10.1016/j.jtos.2017.05.003.
   PubMed Web of Science ®Google Scholar
• Singh S, Narang P, Vashist U, Mittal V. Histomorphological changes in lachrymal glands of patients with chronic stevens-johnson syndrome. Cornea. 2019;38(9):e39–e40. doi:10.1097/ICO.0000000000002037.
   PubMed Web of Science ®Google Scholar