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Effect of pharmacological treatment with mimetic peptide of annexin A1 protein in a model of ocular allergy

Grant number: 12/10637-3
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2012
Effective date (End): July 31, 2013
Field of knowledge:Biological Sciences - Morphology - Histology
Principal Investigator:Cristiane Damas Gil
Grantee:Teresa Raquel de Moraes Andrade
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Annexin A1 (ANXA1) is a 37kDa protein involved in the inhibition of eicosanoids and phospholipase A2 synthesis, induced by glucocorticoids, which confers its anti-inflammatory properties. However, the expression of ANXA1 in normal and inflamed ocular tissues has been little studied. Allergic conjunctivitis (AC) is an immune complex disease involving mast cell degranulation in the conjunctiva and the release of inflammatory mediators and cytokines that cause the infiltration of inflammatory cells in this tissue. This inflammation is the main contributing factor for many ocular disorders and may lead to decreased visual acuity and even blindness. Generally, in the treatment of intraocular inflammation, glucocorticoids are administered and their side effects stimulate the search for new therapeutic strategies. Using an experimental model of AC, we will study the expression and mechanism of action of endogenous ANXA1 in the ocular tissues of mice. Animals will be immunized (days 0 and 7) s.c. with ovalbumin (OVA; 5 µg) and on days 14, 15, and 16, they will receive direct instillation into the conjunctival sac of OVA (250 µg) in 10 µl of PBS. Another group of sensitized animals will be pretreated s.c. in days 14-16 with Ac2-26 peptide (ANXA12-26, N-terminal region of ANXA1; 100 µg per animal) or dexamethasone (0.5 mg/kg), diluted in 0.1 mL of PBS. The Control group will receive only PBS. After 24 hours of the last challenge with OVA, animals will be anesthetized, underwent cardiac puncture to collect blood and the tear fluid and, subsequently, killed by cervical dislocation for enucleation of the eyes and the dissection of spleen and lymph nodes. The studies will be conducted through: histopathological and quantitative analysis of inflammatory cells in ocular tissues and blood, immunohistochemistry, and western blotting to detect ANXA1 expression in ocular tissues, spleen, and lymph nodes, and; levels of IgE in the blood. The results may indicate the mechanism of action of ANXA1 in ocular allergic inflammatory processes and provide new therapeutic options.(AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
GIMENES, ALEXANDRE D.; ANDRADE, TERESA RAQUEL M.; MELLO, CLAUDIA B.; RAMOS, LISANDRA; GIL, CRISTIANE D.; OLIANI, SONIA M.. Beneficial effect of annexin A1 in a model of experimental allergic conjunctivitis. EXPERIMENTAL EYE RESEARCH, v. 134, p. 24-32, . (12/10637-3)

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