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J. P. Gierow, S. K. Carlsson, S. F. Hamm-Alvarez, K. Wu; Up-Regulation of A2 Receptors in the Male NOD Mouse Dry Eye Model. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4139.
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Studies in our laboratory have previously shown the presence of both the adenosine A1 receptor (Exp. Eye Res 86: 110, 2008) and the A2a and A2b receptors in rabbit lacrimal gland (Invest. Ophthalmol. Vis. Sci. 49: E-abstract p2449, 2008). Since adenosine also has been shown to have anti-inflammatory properties (Trends Immunol. 25:33-39, 2004) it was of interest to examine the presence of adenosine receptors in a dry eye model, the male NOD mouse (Invest. Ophthalmol. Vis. Sci. 49: E-abstract p425: 2008).
Sectioned cryonic lacrimal gland from 4, 8, and 12 week old mice were stained for immunohistochemistry using primary antibodies against the A2a and A2b receptors, and analyzed by confocal microscopy. Microarrays (ABI Mouse Genome Survey Microarray) were performed on lacrimal gland RNA isolated, in triplicates, from pooled 12 week old male NOD and Balb/c mice respectively.
Immunohistochemistry indicated the presence of A2a and A2b receptors in both NOD and Balb/c mice. The most intense staining was observed for the A2a receptor in 12 week old male NOD mouse lacrimal gland compared to the matched Balb/c, whereas only minor, variable differences between the two strains were observed for the staining against the A2b receptor. These results were confirmed by the microarray studies where a 2.7-fold increase (p<0.01) of the A2a receptor expression was observed in the NOD mouse lacrimal gland over the Balb/c mouse. A 1.3-fold increase (p<0.05) was observed for the A2b receptor in the NOD system.
Our results show that both the protein and RNA expression of the A2a receptor is up-regulated in the 12 week old male NOD mouse lacrimal gland compared to the Balb/c control making it a potential target for a future treatment regime for dry eye disorders.
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