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Kokoro sano, Motoko Kawashima, Takaaki Inaba, Akiko Ito, Shusaku Tamaki, Tetsuya Kawakita, Shigeto Shimmura, Kazuo Tsubota; Tear Volume Change By A Single Intraperitoneal Injection With AICAR In Mice. Invest. Ophthalmol. Vis. Sci. 2012;53(14):623.
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AMP-activated protein kinase (AMPK) plays a key role in the regulation of energy homeostasis in various organs including muscles and liver. We investigated the effects of AMPK activator, 5-Aminoimidazole-4-carboxyamide ribonucleoside (AICAR) on tear secretion in mice.
Male C57BL/6JJc1 mice received a single intraperitoneal injection of 250mg/kg AICAR (n=10) or no treatment as a control (n=10). Tear secretion was measured by cotton threads (Zone Quick) for 30 seconds at the following time-course (pre-administration and at 0.5,1, 4, 6, and 24 hours after administration). For gene expression analysis, the same treatment was performed using different mice (n=6,at each time point). Lacrimal glands were removed from mice, total RNA was extracted, and real time PCR was performed for Nicotinamide phosphoribosyltransferase(Nampt).
The tear volume increased with AICAR treatment. At 4 and 6 hours after AICAR injection, the tear volume was significantly larger (5.5±3.5mm, 5.3±3.8mm) than the control (4.75±3.7mm,4.0±3.0mm) (p=0.01,p<0.01, respectively). After 24 hours, no significant differences were observed between the 2 groups. In the real time PCR, Nampt expression increased time-dependently up to 6 hours.
A single dose of AICAR leads to increase of tear volume. The results suggest that pharmacological activation of AMPK may be a potential therapy for dry eye disease.
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