Sources In Time JUAN MURUBE, MD, PHD, EDITOR
When Were the Goblet Cells of the Conjunctiva First Described? JUAN MURUBE, MD, PHD oblet cells were described for the first time by Jacob Henle in 1837 in the mucosa of the small intestine.1 Schulze (1866) gave these glands the German name Becherzellen, referring to the morphology of these glands and not to their secretion, about which he was dubious.2 Becherzellen was translated in English as goblet cells and in Latin and the Romance-derived languages as cellulae caliciformes. Mucinic glands in the ocular conjunctiva had been previously mentioned in the 1850’s by Gerlach3 and Leydig,4 but these mentions were imprecise and indefinite. In 1853, Sappey noted the presence of glands in the conjunctiva, to which he attributed a mucous secretion and hypothesized to be like the Harderian glands of animals.5 However, Krause believed that the glands described by Sappey were the accessory aqueous glands first found by his father Carl Krause, because they were preferentially localized in the conjunctival fornices and they numbered between 8 and 25.6 The first persons to clearly find goblet cells in the human conjunctiva were Henle (1866) 7 and Stieda (1867).8 These glands have a cryptic form with various architectures (tubular, reticular, saccular, arboriform, intraepithelial). They are known today as mucous crypts of Henle, in
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Juan Murube, MD, PhD, Moralazzal 43, Madrid E-28034, Spain. ©2003 Ethis Communications, Inc. All rights reser ved.
order to differentiate them from the exposed mucin-producing cells. The mucous crypts of Henle were considered by some to be artifacts due to histological cuts or distortions caused by conjunctival scarring.9,10 Many of the researchers of that time believed that tubulous and superficial
production of mucin.20 With the advice of Leber, in whose laboratory he worked, Green induced conjunctivitis in rabbits and observed that goblet cells did not change significantly. Thus, the belief that goblet cells are normal spread.21 Although it became generally ac-
Figure 1. A piece of tarsal conjunctiva 0.4 mm wide has been cut perpendicularly to the surface and stained with Masson’s trichromic. The goblet cells have a tubular formation, sometimes with the appearance of a goblet or cup, as clearly seen in the last gland on the right.
mucous glands of the conjunctiva were pathological formations of the conjunctiva, caused by chronic irritation of the eye, trachoma, or other conjunctivitis,11–14 but over time (1874–1886), they became accepted as normal structures.15–19 At the end of the 19th century, the normality or abnormality of the tubulous mucinic glands was not yet agreed upon. In 1894, Green documented the presence of goblet cells in the normal conjunctiva of human, pig, dog, cat, sheep, rabbit, rat, mouse, and guinea pig and described their
cepted that most goblet cells are normal structures, the earlier concept that some of them represented new or modified glands created by pathological conditions was maintained by some authors. Although they accepted the evidence of the presence of goblet cells in normal eyes, they believed that goblet cells multiply and change in cases of conjunctivitis and external irritation.22–25 Today, the question is no longer whether conjunctival goblet cells exist or whether they are natural or pathological. We are now directing
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our attention to the different types of goblet cells and their mucins, the functions of each variety of mucin, the specific location of each variety of goblet cell, the role they play in immunologic defense or tear film formation, where their stem cells are, and which are their daughter cell lines. The development of these concepts will be discussed in future essays. 䢇 REFERENCES 1. Henle J. Symbolae ad anatomiam villorum intestinalium, imprimis eorum epithelii et vasorum acteorum; commentatio academica. Berolini, Hirschwald, 1837. Quoted by Virchow H in “Conjunctiva,” Graefe-Saemisch: Handbuch der Augenheilkunde, Vol. I. Leipzig, Engelmann, 1910, p 587 2. Schulze FE. Das Drüsenepithel der Schlauchförmigen Drüsen des Dünnund Dickdarms und die Becherzellen. Zentralbl med Wiss. 1866;4(11):161-4 3. Gerlach J. Handbuch der Gewebelehre des menschlichen Körpers. 2nd ed. Berlin, Hirschwald. 1852, p 471 4. Leydig F. Lehrbuch der Histologie der Menschen und der Tiere. Frankfurt am Main: Meidinger, 1857, p 228 5. Sappey PC. Recherches sur les glandes des paupières. Gaz Méd Paris 1853;33:515-7 and 528-31 6. Krause W. Ueber die Drüsen der Conjunctiva. Zeitschr ration Med 1854;4:337-41
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7. Henle J. Handbuch der systematischen Anatomie des Menschen. Braunschweig, Vol II. F. Vieweg und Sohn, 1866, p 702 8. Stieda L. Ueber den Bau der Augenlidbindehaut des Menschen. Arch mikr Anat 1867;3:357-65 9. Luschka H von. Die Anatomie des Menschen, Vol III. Tübingen, Vieweg und Sohn, 1867, p 369 10. Sattler H. Beitrag zur Kenntniss der normalen Bindehaut des Menschen. Graefes Arch Ophthalmol 1877;23(4):128 11. Kuhnt V. Ueber eine eigenthümliche Form drüsenartiger Gebilde am oberen Augenlid. Klin Monatsbl Augenheilkd 1877;15:117-8 12. Ivanoff A. Beitrage zur pathologischen Anatomie des Trachoms. Communication to the Deutsche Ophthalmologische Geselschaft (Heidelberg, 1878). Quoted by Nuel 1882 (reference 18) 13. Berlin E. Beiträge zur pathologischen Anatomie der Conjunctiva. Klin Monatsb Augenheilkd 1878;16:341-60 14. Jacobson J. Ueber Epithelwucherung und Follikelbildung in der Conjunctiva mit besonderer Berücksichtigung der conjunctivitis granulosa. Graefes Arch Ophthalmol,1879;25:131-75 15. Ciaccio GV. Osservazioni intorno alla struttura della congiuntiva umana, Vol 24. Mem Acad Sci Bologna. 1874 16. Reich M. Zur Histologie der Conjunctiva des Menschen. Graefes Arch
Ophthalmol 1875;21:1-22 17. Baumgarten P. Ueber die tubulösen Drüsen und die Lymphfollikel in der Lidconjunctiva des Menschen. Graefes Arch Ophthalmol 1880;26:122-34 18. Nuel JP. Des glandes tubuleuses pathologiques dans la conjonctive humaine. Ann Ocul (Paris) 1882; 88:5-24 19. Proebsting A. Ein Beitrag zur feineren Anatomie des Lides und der Conjunctiva des Menschen und Affen. Dissertatio Inauguralis. ErlangenMunich, 1886 20. Green CL. Ueber die Bedeutung der Becherzellen der Conjunctiva. Graefes Arch Ophthalmol 1894; 40(1):1-21 21. Greff G. Lehrbuch der pathologischen Anatomie des Auges. Berlin, Hirschwald, 1902 22. Virchow H. Conjunctiva: GraefeSaemisch: Handbuch der Augenheilkunde. Leipzig, Engelmann, 1910 23. Schieck F, Brückner A. Kurzes Handbuch Ophthalmologie, Vol I. Berlin, Springer, 1930, pp 271-80 24. Rintelen F. Augenheilkunde. Basel, Karger, 1961, p 39 25. Podhorányi G. Ueber die Becherzellen der Bindehaut. Graefes Arch Ophthalmol, 1966;169:285-93 Juan Murube is Professor of Ophthalmology, University of Alcala-Madrid, Spain; Chairman of the Department of Ophthalmology, Hospital Ramon y Cajal, Madrid; and President of the Rizal Institute for Research in Ophthalmology.
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