Inflammatory cytokine expression on the ocular surface in the Botulium toxin B induced murine dry eye model.
OBJECTIVE
Inflammation plays an important role in dry eye syndrome. In this study, inflammatory cytokine expression on the ocular surface in the Botulium toxin B (BTX-B) induced mouse dry eye model was investigated.


METHODS
CBA/J mice received an injection of saline or 20 milliunits (mU) of BTX-B into the lacrimal gland. Tear production and corneal fluorescein staining were evaluated in all groups before injection and at 3 time points after. The pro-inflammatory cytokines macrophage inhibitory factor (MIF), interleukin-1beta (IL-1 beta), tumor necrosis factor-alpha (TNF- alpha) and interleukin-6 (IL-6) in conjunctival and corneal epithelium were evaluated by real time quantitative PCR and immunohistochemistry.


RESULTS
BTX-B injected mice showed significantly decreased aqueous tear production and increased corneal fluorescein staining at the 1 week and 2 week time points compared with normal control and saline-injected mice. The BTX-B injected mice mRNA expression levels of TNF-alpha and IL-1beta from conjunctival and corneal epithelial cells increased significantly at two early time points comparing with that of normal and saline injected mice, but IL-1beta returned to normal levels at the 4 week time point. Saline injected mice showed no difference in mRNA expression of TNF-alpha, IL-1beta, MIF, and IL-6 on the ocular surface tissue at all time points. Immunohistochemistry confirmed these findings.


CONCLUSIONS
BTX-B induced mouse model showed decreased aqueous tear production, increased corneal fluorescein staining, and TNF-alpha and IL-1beta increased expression on the ocular surface within one month. The patterns seen appeared to mimic those in humans with non-Sjögren's syndrome keratoconjunctivitis sicca (NS-KCS).
Zhu
Lei
L
Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD 21117, USA.
Shen
Jikui
J
Zhang
Cheng
C
Park
Choul Yong
CY
Kohanim
Sahar
S
Yew
Margaret
M
Parker
John S
JS
Chuck
Roy S
RS
D000818:Animals; D001905:Botulinum Toxins; D003228:Conjunctiva / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003315:Cornea / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000139:chemically induced / Q000378:metabolism*; D005260:Female; D019793:Fluorescein / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects; D007765:Lacrimal Apparatus / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D013666:Tears / Q000187:drug effects / Q000378:metabolism
D016207:Cytokines; D001905:Botulinum Toxins; D019793:Fluorescein