The pathology of dry eye: the interaction between the ocular surface and lacrimal glands.
BACKGROUND
Most dry-eye symptoms result from an abnormal, nonlubricative ocular surface that increases shear forces under the eyelids and diminishes the ability of the ocular surface to respond to environmental challenges. This ocular-surface dysfunction may result from immunocompromise due to systemic autoimmune disease or may occur locally from a decrease in systemic androgen support to the lacrimal gland as seen in aging, most frequently in the menopausal female.


OBJECTIVE
Components of the ocular surface (cornea, conjunctiva, accessory lacrimal glands, and meibomian glands), the main lacrimal gland, and interconnecting innervation act as a functional unit. When one portion is compromised, normal lacrimal support of the ocular surface is impaired. Resulting immune-based inflammation can lead to lacrimal gland and neural dysfunction. This progression yields the OS symptoms associated with dry eye.


METHODS
Restoration of lacrimal function involves resolution of lymphocytic activation and inflammation. This has been demonstrated in the MRL/lpr mouse using systemic androgens or cyclosporine and in the dry-eye dog using topical cyclosporine. The efficacy of cyclosporine may be due to its immunomodulatory and antiinflammatory (phosphatase inhibitory capability) functions on the ocular surface, resulting in a normalization of nerve traffic.


CONCLUSIONS
Although the etiologies of dry eye are varied, common to all ocular-surface disease is an underlying cytokine/receptor-mediated inflammatory process. By treating this process, it may be possible to normalize the ocular surface/lacrimal neural reflex and facilitate ocular surface healing.
Stern
M E
ME
Department of Biological Sciences, Allergan, Inc., Irvine, CA 92713-9534, USA. stern_michael@allergan.com
Beuerman
R W
RW
Fox
R I
RI
Gao
J
J
Mircheff
A K
AK
Pflugfelder
S C
SC
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D015551:Autoimmunity / Q000276:immunology; D001341:Autonomic Nervous System / Q000503:physiopathology; D003228:Conjunctiva / Q000473:pathology*; D003315:Cornea / Q000294:innervation / Q000473:pathology*; D004285:Dogs; D015352:Dry Eye Syndromes / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007765:Lacrimal Apparatus / Q000294:innervation / Q000473:pathology*; D008537:Meibomian Glands / Q000473:pathology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D009883:Ophthalmic Solutions; D013601:T-Lymphocytes / Q000276:immunology
D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D009883:Ophthalmic Solutions