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Anatomy and Histopathology of the Human Lacrimal Gland

Article  in  Cornea · January 2007

DOI: 10.1097/01.ico.0000247220.18295.d3 · Source: PubMed

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 ARTICLE

Anatomy and Histopathology of the Human

Lacrimal Gland
Hiroto Obata, MD, PhD

Pathologic changes of the lacrimal gland decrease the

Purpose: To review the anatomy and histopathologic changes of the
human main lacrimal gland.
Methods: Samples of lacrimal gland including palpebral lobes and
orbital lobes were taken in autopsies, and the relationship between
histopathologic changes and age and sex, as well as histopathologic
differences between palpebral and orbital lobes of the lacrimal gland,
were studied using light microscopy.
Results: Various histopathologic changes were observed in the
human main lacrimal gland as follows: acinar atrophy; periacinar
fibrosis; periductal fibrosis; interlobular ductal dilatation; interlobular
ductal proliferation; lymphocytic infiltration; and fatty infiltration.
Several histopathologic differences exist between the palpebral and
orbital lobes. There were statistically significant correlations between
age and diffuse fibrosis, diffuse atrophy, and periductal fibrosis in the
orbital lobes of women. Diffuse fibrosis and diffuse atrophy in orbital
lobes were more frequently observed in women than in men.
Conclusion: It is speculated that periductal fibrosis is related to
a decrease of tear flow with age and that interlobular ductal dilatation
in palpebral lobes may be caused by stenosis of the excretory duct in
conjunctival fornix. However, the mechanisms of these histopatho-
logic changes in the human main lacrimal gland are not yet clear.
Key Words: human lacrimal gland, histopathology, aging
(Cornea 2006;25:S82–S89)
quality and quantity of tear fluid and may cause dry eye syn-
drome. Previous histopathologic studies of the human lacrimal
gland have been few.1–3 The human main lacrimal gland com-
prises palpebral and orbital lobes; however, the reports published
to date did not state which portions of palpebral and orbital lobes
and what size samples of lacrimal gland had been excised.
Consequently, differences between palpebral and orbital lobes
were not studied, and the extent of histologic changes was in-
sufficiently evaluated. Therefore, in this autopsy study, both
lobes were completely removed, and the extent of various histo-
pathologic changes in each lobe of the main lacrimal gland was
studied in detail. Reported here are the results, as well as those
previously published,4 and in addition, a review is presented of
the anatomy and histopathology of the human lacrimal gland
based on the author’s experience of approximately 200 samples
of human lacrimal glands obtained at autopsy.
ANATOMY OF THE HUMAN LACRIMAL GLAND
The human lacrimal gland consists of the main lacrimal
gland and the accessory lacrimal gland. The main lacrimal
gland comprises palpebral and orbital lobes, which are con-
tinuous with each other at the lateral edge of the aponeurosis of
levator palpebrae superioris (Fig. 1).5–7 The orbital lobe is
approximately twice as large as the palpebral lobe and lies in

T he ocular surface is protected by tear fluid supplied from

the gland system comprising the main and accessory
lacrimal gland, meibomian gland, and goblet cell of conjunc-
tiva. Normal function of the gland system promotes a healthy
ocular surface and maintains normal visual function. Although
every component of tear fluid from the gland system is
necessary for a healthy ocular surface, the major source of tear
fluid is the lacrimal gland.

Accepted for publication June 6, 2006.

From the Department of Ophthalmology, School of Medicine, Jichi Medical
University, Tochigi, Japan.
The author states that he has no proprietary interest in the products named in
this article.
Reprints: H. Obata, Department of Ophthalmology, School of Medicine, Jichi
Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi 329-0498,
Japan (e-mail: obatah@jichi.ac.jp).
Copyright Ó 2006 by Lippincott Williams & Wilkins
FIGURE 1. Anatomy of the human main lacrimal gland in the
right orbit. The main lacrimal gland comprises the palpebral
and orbital lobes, which are continuous with each other at the
lateral edge of the aponeurosis of levator palpebrae superioris.
The palpebral lobe is in contact with the conjunctival fornix. LR,
lateral rectus muscle; IO, inferior oblique muscle.

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Cornea  Volume 25, Supp. 1, December 2006 Histopathology of the Lacrimal Gland

FIGURE 2. Entire main lacrimal glands from left and right orbits. FIGURE 5. Secretory granules of acinar cells. Secretory granules
Palpebral lobes are above and orbital lobes below dotted lines. of acinar cells are positive for PAS staining (original magnifi-
R, right; L, left. Reprinted from Obata et al.4 Copyright Ó 1995, cation: 3132).
with permission from American Academy of Ophthalmology.

FIGURE 6. Immunostaining of a-SMA. Myoepithelial cells are

inconspicuous in routine H&E sections, but immunostaining of
FIGURE 3. Normal histology of the human lacrimal gland. The
a-SMA reveals basket-like structures around acini. The small
lobule has many acini and intralobular ducts (arrows on the left).
artery is also positive for a-SMA as shown in the top left corner
Interlobular ducts (arrows on the right) and an artery (A) are seen
(original magnification: 3132).
in the interlobular connective tissue (original magnification: 333).

FIGURE 4. The palpebral lobe of the lacrimal gland is in contact FIGURE 7. Immunostaining of immunoglobulin (Ig)A. Most
with the fornix of conjunctiva. Excretory ducts (arrows) open to plasma cells (arrows) in stroma are positive for anti-IgA
the conjunctival epithelial surface (original magnification: 320). antibody (original magnification: 3132).

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Obata Cornea  Volume 25, Supp. 1, December 2006

the lacrimal fossa on the anterior lateral area of the orbit. The
palpebral lobe lies below the aponeurosis of levator palpebrae
superioris and is in contact with the superior and lateral fornix
of conjunctiva. Excretory ducts coming from the palpebral and
orbital lobes open into the superior conjunctival fornix. The
main lacrimal gland measures approximately 20 3 25 mm and
has a thickness of 3 mm in the palpebral lobe and 5 mm in the
orbital lobe (Fig. 2). The size of the main lacrimal gland varies
individually to some degree.
The accessory lacrimal gland is a small or mini lacrimal
gland located in the lamina propria of conjunctiva and is divided
into 2 anatomic groups: the glands of Krause and glands of
Wolfring.5,6 Both types of glands are too small to identify in liv-
ing individuals. The glands of Krause are located in the lamina
propria of fornix and the glands of Wolfring are in the edge of the
tarsus. The ducts of both glands open on the conjunctival surface.
HISTOLOGY OF THE HUMAN MAIN
LACRIMAL GLAND
Light Microscopy
The lacrimal gland is an exocrine gland, as well as
a mammary gland and a salivary gland. The main lacrimal
gland comprises many lobules separated from one another by
loose connective tissue.5–7 Each lobule has many acini and
intralobular ducts (Fig. 3). The connective tissue contains
interlobular ducts, vessels, nerve fibers, fibroblasts, many
plasma cells, and a few lymphocytes. Interlobular ducts finally
become approximately 12 excretory ducts, which open into the
fornix of conjunctiva (Fig. 4). Because of its anatomic
characteristics, the orifices of excretory ducts can be occluded
in severe ocular surface diseases with keratinization such as
Stevens-Johnson syndrome and cicatricial pemphigoid. In

FIGURE 8. Transmission electron micrograph of a human lacrimal gland. Many secretory granules and well-developed rough
endoplasmic reticulum are seen in acinar cells. Junctional complex (zonula occludens and zonula adherence followed by scattered
desmosomes) is present on the lateral membrane of acinar cells. Inset, Myofilaments in myoepithelial cell. SG, secretory granules;
N, nucleus; rER, rough endoplasmic reticulum; L, lumen; ME, myoepithelial cell; mf, myofilaments.

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Cornea  Volume 25, Supp. 1, December 2006
FIGURE 9. Scanning electron micro-
graph taken after removal of con-
nective tissue by KOH-collagenase
digestion method. A, Many acini
appear like a bunch of grapes. B, In
higher magnification, the capillary
network can be seen around acini.
other words, lacrimal secretion can be physically blocked in
ocular surface disease with pathologic damaged epithelia.
Therefore, ocular surface epithelia should be maintained
healthy for lacrimal secretion.
The acinus comprises pyramid-shaped acinar cells with
central lumen. Acinar cells have many periodic acid-Schiff
(PAS)-positive secretory granules and basally located nuclei
(Fig. 5). Myoepithelial cells are distributed surrounding the
acini and intercalated ducts. Myoepithelial cells have stellate,
multiprocessed morphology, and their contraction may play
a role in expelling secretory products from glandular lumina
into ducts. Myoepithelial cells, as the name implies, have
structural features of both epithelial and smooth muscle cells.
They express both a-smooth muscle actin (a-SMA) and
cytokeratin 5, which can be used as markers to identify these
cells.8 Myoepithelial cells are generally inconspicuous in
routine hematoxylin and eosin (H&E) sections and are best
observed by immunohistochemistry (Fig. 6).
The ducts comprise 2 to 3 layers of epithelial cells.
Ductal epithelial cells in the superficial layer have granules in
cytoplasm that differ from secretory granules in acinar cells.5
Intralobular and interlobular ducts lack myoepithelial cells.
Plasma cells in connective tissue produce IgA and are
involved in the formation of secretory IgA in tear fluid (Fig. 7).
Secretory IgA is the best-defined effector component of the
mucosal immune system.
Electron Microscopy
As seen by transmission electron microscopy, the human
main lacrimal gland exhibits numerous electron-dense secre-
tory granules and well-developed rough endoplasmic retic-
ulum (Fig. 8). Junctional complex, zonula occludens (tight
junction), and zonula adherence, followed by scattered desmo-
somes, are present on the lateral membrane of acinar cells.5
Myoepithelial cells are situated between the acinar cells and
the basement membrane and display numerous myofilaments.
Scanning electron microscopy after removal of the
connective tissue by KOH-collagenase digestion method re-
veals numerous acini showing a grape-like structure (Fig. 9A).
It is observed that capillary vessels run between the acini
forming a network (Fig. 9B). Abundant blood supply may be
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Histopathology of the Lacrimal Gland
crucial for the synthesis of secretory granules and watery
secretion.
HISTOLOGY OF THE HUMAN ACCESSORY
LACRIMAL GLAND
Basically, the accessory lacrimal gland is histologically
and histochemically the same as the main lacrimal gland.8,9
It is not clear how much the accessory lacrimal gland con-
tributes to total tear volume. One interesting study reported
that tears from accessory lacrimal glands were sufficient to
maintain a stable tear layer on a monkey cornea model of uni-
lateral main lacrimal gland removal, suggesting that basal tear
flow is made up of fluid from both main and accessory lacrimal
glands.10 Another valuable case study reported that kerato-
conjunctivitis sicca developed immediately after palpebral
dacryoadenectomy in a healthy 43-year-old woman, indicating
that the main lacrimal gland is an indispensable part of the tear
system and secretion of the accessory lacrimal gland is unable
to prevent tear insufficiency.11
HISTOPATHOLOGY OF THE HUMAN MAIN
LACRIMAL GLAND
The following histopathologic changes were observed in
the human main lacrimal gland obtained postmortem: acinar
atrophy; periacinar fibrosis; periductal fibrosis; interlobular
ductal dilatation; interlobular ductal proliferation; lymphocytic
infiltration; and fatty infiltration. In my previous statistical
study of 80 samples of lacrimal glands,4 the following criteria
were used to grade fibrosis and atrophy: ‘‘focal’’ was defined
as change present only within 1 lobular architecture, ‘‘lobular’’
as change present in less than 50% of lobules/section,
and ‘‘diffuse’’ as more than 50% change. Representative
microphotographs are shown in Figures 10–15. These
histopathologic changes were often associated with each other
in the same specimen (eg, lobular atrophy, lobular fibrosis, and
periductal fibrosis are all present in Figure 16). As for the
prevalence of various histopathologic findings in my previous
study,4 the most common finding was periductal fibrosis in
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FIGURE 10. Focal atrophy without fibrosis. Palpebral lobe section
from a 51-year-old man. Acinar atrophy is present in part of
1 lobule. Atrophic acini look like intralobular ducts. Eosinophilic
amorphous material, interpreted as the stasis of tear fluid, is
present in some lumens (original magnification: 340).
FIGURE 11. Lobular atrophy without fibrosis. Palpebral lobe
section from a 44-year-old man. Acinar atrophy covers the
whole of 1 lobule but no periacinar fibrosis is present.
Eosinophilic amorphous material is present in lumens of the
dilated intralubular ducts. Normal acini are present on the left
side of the section (original magnification: 325). Reprinted
from Obata et al.4 Copyright Ó 1995, with permission from
American Academy of Ophthalmology.
FIGURE 12. Lobular atrophy with lobular fibrosis. Palpebral lobe
section from a 74-year-old man. Both acinar atrophy and
periacinar fibrosis are present throughout 1 lobule. Normal acini
are present on the left side of the section (original magnification:
333). Reprinted from Obata et al.4 Copyright Ó 1995, with
permission from American Academy of Ophthalmology.
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FIGURE 13. Periductal fibrosis. Orbital lobe section from a 62-
year-old man. Hyalinized thick connective tissue is present
around the interlobular duct (arrows). Ductal epithelium is
atrophic (original magnification: 350). Reprinted from Obata
et al.4 Copyright Ó 1995, with permission from American
Academy of Ophthalmology.
FIGURE 14. Interlobular ductal dilatation. Palpebral lobe
section from a 58-year-old woman. Cystic dilatation of
interlobular ducts with atrophic ductal epithelium is present.
Stasis of tear fluid is seen as eosinophilic amorphous material in
cystic ducts. This may be caused by stenosis of the excretory
duct in the fornix of conjunctiva (original magnification: 310).
FIGURE 15. Periductal lymphocytic infiltration. Palpebral lobe
section from a 64-year-old woman. Lymphocytic infiltration
can be seen around the intralobular duct (original magnifica-
tion: 350). Reprinted from Obata et al.4 Copyright Ó 1995,
with permission from American Academy of Ophthalmology.
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FIGURE 16. Lobular atrophy, lobular fibrosis, and periductal
fibrosis. Orbital lobe section from a 68-year-old man. Acinar
atrophy, periacinar fibrosis, and periductal fibrosis are present
(original magnification: 313.3). Reprinted from Obata et al.4
Copyright Ó 1995, with permission from American Academy
of Ophthalmology.
FIGURE 18. Histopathologic differences between palpebral
and orbital lobes. Palpebral lobe shows normal histology (A);
however, the orbital section shows acinar atrophy and
periacinar atrophy (B) in a 77-year-old woman at the same
magnification (original magnification: 350).
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Histopathology of the Lacrimal Gland
FIGURE 17. Immunostaining of lysozyme. Immunoreactivity of
lysozyme is not present in atrophic acinar cells but is present in
normal acinar cells (original magnification: 3132).
FIGURE 19. Histologic findings of age-related changes. A,
Normal histologic finding from a 17-year-old man. B,
Histologic finding of an 87-year-old woman shows acinar
atrophy and periductal fibrosis (arrows) at the same magni-
fication (original magnification: 350). Reprinted from Obata
et al.4 Copyright Ó 1995, with permission from American
Academy of Ophthalmology.
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Obata
orbital lobes (35.0%), and the least common finding was
interlobular ductal dilatation in palpebral lobes (3.8%).
Acinar Atrophy
Acinar atrophy is defined as a diminished volume of
cells under certain pathologic conditions subsequent to normal
cellular development. The findings of acinar atrophy suggest
lacrimal gland dysfunction. As an example of this dysfunction,
immunostaining of the major tear fluid protein lysozyme is
shown in Figure 17. Immunoreactivity of lysozyme was not
present in atrophic acinar cells, whereas it was detected in
normal acinar cells. Acinar atrophy is probably related to
a decrease of tear proteins as a consequence of aging.
Periacinar Fibrosis
It is commonly believed that fibrosis of the exocrine
gland results from a decrease of acinar elements.12 However, in
certain pathologic conditions such as chronic graft-versus-host
disease (GVHD), stromal fibroblasts are actively involved in
the pathogenic process of the lacrimal gland.13
Periductal Fibrosis
Periductal fibrosis can be considered an important factor
related to decreased outflow of tear fluids (Fig. 13). Atrophic
ductal epithelium is often associated with periductal fibrosis.
Because both ductal epithelial cells and acinar cells are
responsible for electrolyte and water secretion,14,15 periductal
fibrosis and atrophy of ductal epithelial cells may interfere
with normal physiological function of the ducts.
Interlobular Ductal Dilatation
Another interesting ductal pathologic change of great
importance is interlobular ductal dilatation in palpebral lobes
(Fig. 14). It seems that stenosis or obstruction of orifices of the
excretory duct in the fornix of conjunctiva causes cystic
dilatation of interlobular ducts in palpebral lobes, indicating
physical obstruction of tear fluid outflow. Stenotic or obstruc-
tive changes in the ducts may be caused by various types of
subclinical conjunctivitis because the palpebral lobes are in
anatomic contact with the fornix of conjunctiva. As mentioned
above, conjunctival epithelia must be kept healthy for normal
lacrimal gland function.
Lymphocytic Infiltration
Focal lymphocytic infiltration of lacrimal glands was
observed in my autopsy series in patients in whom there was
no autoimmune disease, as confirmed in previous studies (Fig.
15).16,17 In Sjögren syndrome, the earliest histologic finding in
salivary glands has been described as periductal lymphocytic
infiltration.18 Focal lymphocytic infiltration of the lacrimal
gland suggests subclinical dacryoadenitis. However, it is not
clear whether this is an early finding of lymphoproliferative
disorders including Sjögren syndrome, reactive lymphoid
hyperplasia, and malignant lymphoma.
Histopathologic Differences Between
Palpebral and Orbital Lobes
Interestingly, several histopathologic differences exist
between palpebral and orbital lobes as previously described.4
Lobular fibrosis, lobular atrophy, diffuse fibrosis, diffuse atrophy,
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Cornea  Volume 25, Supp. 1, December 2006
periductal fibrosis, lymphocytic foci, and fatty infiltration were
significantly more frequent in orbital lobes, whereas in-
terlobular ductal dilatation was significantly more frequent in
palpebral lobes. A representative microphotograph of these
histopathological differences is shown in Figure 18. The
reasons for these differences are not clear. Fatty infiltration in
orbital lobes may be related to the lobe’s anatomic char-
acteristics because the orbital lobe is surrounded by orbital
adipose tissue. At the beginning of this study, it was supposed
that palpebral lobes were more susceptible to undergoing
pathologic changes than orbital lobes because palpebral lobes
are in anatomic contact with the conjunctival fornix and can be
influenced by foreign stimulation. It is not known whether
structural and functional differences exist. This author spec-
ulates that there are some anatomic differences (eg, difference
of innervation in these lobes).
Age-Related Changes of the Human
Lacrimal Gland
The relation between histopathologic changes and age
and sex was statistically analyzed. Full details are presented in
a previous paper.4 There were statistically significant corre-
lations between age and diffuse fibrosis, diffuse atrophy, and
periductal fibrosis in orbital lobes of women and periductal
fibrosis in palpebral lobes of men. Diffuse fibrosis and diffuse
atrophy in orbital lobes were more frequently observed in
women than in men. This result is of great importance because
it suggests a relationship with dry eye that is mostly encoun-
tered in postmenopausal women. As examples of age-related
changes, histologic findings in a 17-year-old man and an
87-year-old woman are shown in Figure 19, where it can be
clearly seen that the acinar area in the lacrimal glands of the
elderly woman is much smaller than that of the young man
(microphotographs taken at same magnification).
CONCLUSION
Various histopathologic changes of human lacrimal
glands obtained postmortem were noted, among which diffuse
fibrosis, diffuse atrophy, and periductal fibrosis in the orbital
lobes of women were age related. Ductal pathologic changes
such as periductal fibrosis and interlobular ductal dilatation
may be important factors in the decrease of tear fluid outflow.
Moreover, it is interesting that there are histopathologic
differences between the palpebral and orbital lobes of the
lacrimal gland.
The etiologic mechanisms of these various histopatho-
logic changes remain unclear. A wide variety of causative fac-
tors such as aging, apoptosis, sex steroid hormone, pituitary-
dependent factors, neurotrophic factors, autoimmune reaction,
and infection are assumed to be possibly involved in lacrimal
gland pathology.19–27 In living organs, cell-to-cell, cell-to-
matrix, and cell-to-environment interactions are intricately
intertwined with pathologic changes. For ophthalmologists
and ophthalmic pathologists, I hope that this review of histo-
pathologic changes of the human lacrimal gland provides
some clues to understanding the pathogenic mechanisms of the
diseased lacrimal gland.
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REFERENCES
1. Williamson J, Gibson AAM, Wilson T, et al. Histology of the lacrimal
gland in keratoconjunctivitis sicca. Br J Ophthalmol. 1973;57:852–858.
2. Damato BE, Allan D, Murray SB, et al. Senile atrophy of the human
lacrimal gland: the contribution of chronic inflammatory disease. Br J
Ophthalmol. 1984;68:674–680.
3. Roen JL, Stasior OG, Jakobiec FA. Aging changes in the human lacrimal
gland: role of the ducts. CLAO J. 1985;11:237–242.
4. Obata H, Yamamoto S, Horiuchi H, et al. Histopathologic study of
human lacrimal gland: Statistical analysis with special reference to aging.
Ophthalmology. 1995;102:678–686.
5. Iwamoto T, Jakobiec FA. Lacrimal glands. In: Jakobiec FA, ed. Ocular
Anatomy, Embryology, and Teratology. Philadelphia, PA: Harper & Row;
1982:761–781.
6. Bron AJ, Tripathi RC, Tripathi BJ. The ocular appendages: eyelids,
conjunctiva and lacrimal apparatus. In: Bron AJ, Tripathi RC, Tripathi BJ,
eds. Wolff’s Anatomy of the Eye and Orbit. 8th ed. London: Chapman &
Hall Medical; 1997:30–84.
7. Snell RS, Lemp MA. Lacrimal apparatus. In: Clinical Anatomy of the Eye.
2nd ed. Malden, MA: Blackwell Science; 1998:114–124.
8. Vigneswaran N, Wilk CM, Heese A. Immunohistochemical character-
ization of epithelial cells in human lacrimal glands. I. Normal major and
accessory lacrimal glands. Graefes Arch Clin Exp Ophthalmol. 1990;228:
58–64.
9. Obata H, Horiuchi H, Dobashi Y, et al. Immunohistochemical localization
of epidermal growth factor in human main and accessory lacrimal glands.
Jpn J Ophthalmol. 1993;37:113–121.
10. Maitchouk DY, Beuerman RW, Ohta T, et al. Tear production after
unilateral removal of the main lacrimal gland. Arch Ophthalmol. 2000;
118:246–252.
11. Scherz W, Dohlman CH. Is the lacrimal gland dispensable? Kerato-
conjunctivitis sicca after lacrimal gland removal. Arch Ophthalmol. 1975;
93:281–283.
12. Scott J. Structure and function in aging human salivary glands.
Gerodontology. 1986;5:149–158.
13. Ogawa Y, Yamazaki K, Kuwana M, et al. A significant role of stromal
fibroblasts in rapidly progressive dry eye in patients with chronic GVHD.
Invest Ophthalmol Vis Sci. 2001;42:111–119.
14. Alexander JH, van Lennep EW, Young JA. Water and electrolyte secretion
by the exorbital lacrimal gland of the rat studied by micropuncture and
catheterization techniques. Pflugers Arch. 1972;337:299–309.
q 2006 Lippincott Williams & Wilkins
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Histopathology of the Lacrimal Gland
15. Dartt DA. Physiology of tear production. In: Lemp MA, Marquardt R,
eds. The Dry Eye: A Comprehensive Guide. Berlin: Springer-Verlag;
1992:65–99.
16. Waterhouse JP. Focal adenitis in salivary and lacrimal glands. Proc R Soc
Med. 1963;56:911–918.
17. Nasu M, Matsubara O, Yamamoto H. Post-mortem prevalence of
lymphocytic infiltration of the lacrymal gland: a comparative study
in autoimmune and non-autoimmune diseases. J Pathol. 1984;143:
11–15.
18. Cotran RS, Kumar V. Sjögren’s syndrome. In: Cotran RS, Kumar V,
Collins T, eds. RobbinsÕ Pathologic Basis of Disease. 6th ed. Philadelphia,
PA: WB Saunders; 1999;225–226.
19. Rios JD, Horikawa Y, Chen LL, et al. Age-dependent alterations in mouse
exorbital lacrimal gland structure, innervation and secretory response.
Exp 3Eye Res. 2005;80:477–491.
20. Azzarolo AM, Wood RL, Mircheff AK, et al. Androgen influence on
lacrimal gland apoptosis, necrosis, and lymphocytic infiltration. Invest
Ophthalmol Vis Sci. 1999;40:592–602.
21. Sullivan DA, Wickham LA, Rocha EM, et al. 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.
22. Azzarolo AM, Bjerrum K, Maves CA, et al. Hypophysectomy-induced
regression of female rat lacrimal glands: partial restoration and
maintenance by dihydrotestosterone and prolactin. Invest Ophthalmol
Vis Sci. 1995;36:216–226.
23. Nyugen DH, Beuerman RW, Thompson HW, et al. Growth factor and
neurotrophic factor mRNA in human lacrimal gland. Cornea. 1997;16:
192–199.
24. Nyugen DH, Beuerman RW, Toshida H. The effects of sensory and
parasympathetic denervation on the kinases and initiation factors
controlling protein synthesis in the lacrimal gland. Adv Exp Med Biol.
2002;506:65–70.
25. Jabs DA, Prendergast RA, Whittum-Hudson JA. Pathogenesis of
autoimmune lacrimal gland disease in MRL/MPJ mice. Adv Exp Med
Biol. 2002;506:771–776.
26. Zhu Z, Stevenson D, Schechter JE, et al. Lacrimal histopathology and
ocular surface disease in a rabbit model of autoimmune dacryoadenitis.
Cornea. 2003;22:25–32.
27. Obata H, Yamagami S, Saito S, et al. A case of acute dacryoadenitis
associated with herpes zoster ophthalmicus. Jpn J Ophthalmol. 2003;
47:107–109.
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