Dry eye-induced conjunctival epithelial squamous metaplasia is modulated by interferon-gamma.
OBJECTIVE
To investigate the role of interferon (IFN)-gamma in the pathogenesis of conjunctival squamous metaplasia in dry eye.


METHODS
Experimental dry eye was created by subjecting C57BL/6 and IFN-gamma-knockout mice to desiccating environmental stress for 5 or 10 days. T-cell antigens and IFN-gamma were detected by immunohistochemistry. Goblet cells were counted in periodic acid Schiff (PAS)-stained sections. Expression of small, proline-rich protein (SPRR)-2 was evaluated by confocal microscopy. Tear IFN-gamma was measured by immunobead assay.


RESULTS
Dry eye promoted migration of CD4+ T cells and IFN-gamma+ cells into goblet cell zones of the conjunctiva and increased the concentration of IFN-gamma in tears. This migration was accompanied by progressive goblet cell loss and an increase in SPRR-2 expression in the conjunctival epithelium. A significant inverse correlation was observed between the density of infiltrating CD4+ T cells and goblet cells. Dry eye had no effect on conjunctival goblet cell density in IFN-gamma-knockout mice; however, exogenous administration of IFN-gamma significantly decreased goblet cell density after 5 days.


CONCLUSIONS
Conjunctival epithelial response to experimental dryness is related to the degree of CD4+ T-cell infiltration and the level of IFN-gamma production. These findings suggest that IFN-gamma plays a pivotal role in promoting conjunctival squamous metaplasia in dry eye, and they provide insight into the immune pathogenesis of keratoconjunctivitis sicca.
De Paiva
Cintia S
CS
Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas 77030, USA.
Villarreal
Arturo L
AL
Corrales
Rosa M
RM
Rahman
Hassan T
HT
Chang
Victor Y
VY
Farley
William J
WJ
Stern
Michael E
ME
Niederkorn
Jerry Y
JY
Li
De-Quan
DQ
Pflugfelder
Stephen C
SC
D019264:Adoptive Transfer; D000818:Animals; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D002452:Cell Count; D002465:Cell Movement / Q000502:physiology; D003228:Conjunctiva / Q000473:pathology*; D055233:Cornified Envelope Proline-Rich Proteins; D015352:Dry Eye Syndromes / Q000150:complications* / Q000276:immunology; D019084:Fluorescent Antibody Technique, Indirect; D020397:Goblet Cells / Q000473:pathology; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000494:pharmacology / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D008679:Metaplasia / Q000209:etiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D011498:Protein Precursors / Q000378:metabolism; D011994:Recombinant Proteins; D013666:Tears / Q000378:metabolism
D055233:Cornified Envelope Proline-Rich Proteins; D008565:Membrane Proteins; D011498:Protein Precursors; D011994:Recombinant Proteins; C101744:SPRR2A protein, human; D007371:Interferon-gamma