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YASUHISA TANAKA, Takaaki Inaba, Kazuo Tsubota; Evaluation of the SIRT2 Deficient Mice as Dry Eye Model Mice. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4471.
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© ARVO (1962-2015); The Authors (2016-present)
Sirtuins (SIRTs) are nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylases which play important roles in modulating the aging process, metabolism and longevity. SIRTs are important genes regulating the physiological function. Various diseases are caused by aging, SIRTs are an important regulatory factor, of protein modification. The change of various factors and the progression of dry eye syndrome are caused by aging, the involvement of SIRT is considered as one of the causes. Here, we focused on SIRT2 gene which is related to cellular senescense. We investigate the tear secretion and histopathological analysis and evaluate the possibility of whether SIRT2 deficient mice can be used as a dry eye model mice.
SIRT2 deficient mice were used in all experiments. As comparison, wild-type and SIRT2 hetero deficient mice were used. The tear volume was measured by the phenol red thread into nasal side of the eyelid margin for 30 seconds once every two weeks. The length of the color change was then measured. The mice were sacrificed and the lacrimal glands were removed. Total protein was extracted from the lacrimal glands of mice and evaluated by western blotting. Histopathological analysis was performed to analyze tissue sections using an optical microscopy after hematoxylin and eosin (H/E) staining.
SIRT2 protein expression was shown in the lacrimal glands of wild type mice. Western blotting analysis confirmed a complete disruption of SIRT2 expression in the SIRT2 deficient mice. Tear secretion was measured by the phenol red thread test, results showed a tendency to decrease in SIRT2 deficient mice compared to those in control mice at 9-30 weeks old. Moreover, H/E staining of the lacrimal glands in SIRT2 deficient mice showed histological change with an accelerated aging phenotype.
These results suggested that SIRT2 is important to the functional maintenance of tear secretion and the lacrimal glands. Further analysis of these mice will clarify the molecule of senescence and inflammatory markers on the lacrimal glands function, which in turn, should elucidate the mechanisms of age-related dry eye.
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