Does androgen insufficiency cause lacrimal gland inflammation and aqueous tear deficiency?
OBJECTIVE
The current investigators have shown that androgen treatment suppresses inflammation and stimulates the function of lacrimal glands in mouse models of Sjögren's syndrome. Recently, others have hypothesized that androgen insufficiency induces an autoimmune process in lacrimal tissue, leading to inflammation, a Sjögren's syndrome-like pathology, and aqueous tear deficiency. The purpose of the present study was to test this hypothesis.


METHODS
Lacrimal glands were obtained from adult testicular feminized (Tfm) and control mice; castrated rats, guinea pigs, and rabbits; and castrated rats without anterior or whole pituitary glands and were processed for histology and image analysis. Tear volumes were measured in mice, in patients taking antiandrogen medications, and in age-matched human control subjects.


RESULTS
Tfm mice, which are completely resistant to classical androgen action, did not have increased lymphocyte infiltration in their lacrimal glands or decreased tear volumes. No inflammation was evident in lacrimal tissues of male or female rats, guinea pigs, or rabbits 12 to 31 days after castration, no inflammation existed in rat lacrimal glands 15 to 31 days after orchiectomy and pituitary removal, and no aqueous tear deficiency was apparent in patients receiving antiandrogen therapy.


CONCLUSIONS
Androgen deficiency may promote the progression of Sjögren's syndrome and its associated lacrimal gland inflammation, meibomian gland dysfunction, and severe dry eye. However, androgen insufficiency alone does not cause lacrimal gland inflammation, a Sjögren's syndrome-like pathology in lacrimal tissue, or aqueous tear deficiency in nonautoimmune animals and humans.
Sullivan
D A
DA
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.
Krenzer
K L
KL
Sullivan
B D
BD
Tolls
D B
DB
Toda
I
I
Dana
M R
MR
D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D000728:Androgens / Q000172:deficiency*; D000818:Animals; D005260:Female; D005262:Feminization / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007016:Hypophysectomy; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D007765:Lacrimal Apparatus / Q000473:pathology; D007766:Lacrimal Apparatus Diseases / Q000209:etiology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009919:Orchiectomy; D010052:Ovariectomy; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000502:physiology; D012016:Reference Values; D013666:Tears / Q000187:drug effects / Q000378:metabolism*
D000726:Androgen Antagonists; D000728:Androgens; D011944:Receptors, Androgen