Time course of ocular surface and lacrimal gland changes in a new scopolamine-induced dry eye model
Graefes Arch Clin Exp Ophthalmol. 2008-03-21; 246(6): 857-867
DOI: 10.1007/s00417-008-0784-9
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1. Graefes Arch Clin Exp Ophthalmol. 2008 Jun;246(6):857-67. doi:
10.1007/s00417-008-0784-9. Epub 2008 Mar 21.
Time course of ocular surface and lacrimal gland changes in a new
scopolamine-induced dry eye model.
Viau S(1), Maire MA, Pasquis B, Grégoire S, Fourgeux C, Acar N, Bretillon L,
Creuzot-Garcher CP, Joffre C.
Author information:
(1)Eye and Nutrition Research Group, UMR1129 FLAVIC, ENESAD, INRA, Université de
Bourgogne, Dijon, France.
BACKGROUND: The aim of this study was to set up an animal model of dry eye
showing disturbance in several components of the lacrimal functional unit, and to
describe the time course of the appearance of clinical signs and inflammatory
markers.
METHODS: Dry eye was induced in 6-week-old female Lewis rats by a systemic and
continuous delivery of scopolamine via osmotic pumps implanted subcutaneously. We
first determined the appropriate dose of scopolamine (6, 12.5, or 25 mg/day) for
28 days. In a second set of experiments, we determined markers after 1, 2, 3, 7,
10, 17, or 28 days of a 12.5-mg/day dose. Clinical signs of corneal dryness were
evaluated in vivo using fluorescein staining. MHC II expression and mucin Muc5AC
production were detected on the conjunctival epithelium using immunostaining. The
level of IL-1beta, IL-6, TNF-alpha, and IFN-gamma mRNA was evaluated by real-time
polymerase chain reaction in conjunctiva and exorbital lacrimal gland (LG).
Lipids were extracted from the exorbital LG for fatty acid analysis.
RESULTS: Daily scopolamine doses of 12.5 mg and 25 mg applied for a 28-day period
induced keratitis, a decrease in Muc5AC immunostaining density in the
conjunctival epithelium, and modifications in the fatty acid composition of the
exorbital LG. Animals treated with a 12.5-mg/day dose of scopolamine exhibited an
increase in corneal fluorescein staining after 2, 10, and 28 days. All animals
exhibited unilateral or bilateral keratitis after 17 days. In the conjunctival
epithelium, a significant decrease in Muc5AC immunostaining density was observed
at early and late time points, and MHC II expression tended to be increased after
1, 7, 10, and 28 days, without reaching statistical significance. The levels of
TNF-alpha, IL-1beta and IL-6 mRNA were increased with scopolamine treatment in
both conjunctiva and exorbital LG. Arachidonic acid and the Delta5 desaturase
index were significantly increased in the exorbital LG of dry eye animals at each
time point.
CONCLUSIONS: This systemic and continuous scopolamine-induced model of dry eye in
the rat may represent a helpful tool to investigate moderate dry eye, and makes a
contribution in the field of dry eye study.
DOI: 10.1007/s00417-008-0784-9
PMID: 18357464 [Indexed for MEDLINE]