Abstract
Purpose :
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 SIRTs are considered as one of the causes. Here, we focused on SIRT5 gene which is related to aging, mitochondorial function and metabolism. We investigate the tear secretion, histopathological analysis, related protein expression and metabolome analysis and evaluate the possibility of whether SIRT5 deficient mice can be used as a dry eye model mice.
Methods :
SIRT5 deficient mice were used in all experiments. As comparison, C57/BL6J 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 mice were sacrificed and the lacrimal glands were removed. Histopathological analysis was performed to analyze tissue sections using an optical microscopy after hematoxylin and eosin (H/E) and Oil Red O staining. Lacrimal gland tissue was examined by metabolome analysis, evaluated by Western blotting about nearby changed protein expression.
Results :
Tear secretion was measured by the phenol red thread test, results decreased in SIRT5 deficient mice compared to that in control mice at 10-30 weeks old. Moreover, H/E staining of the lacrimal glands in SIRT5 deficient mice showed histological change with an accelerated aging phenotype, accumulated the lipid droplet in SIRT5 deficient mice. In addition, after comparing the relations of the tear secretion with the metabolism change in the lacrimal gland, the change of the signal about metabolism of the fatty acid including the HMG-CoA was cleared.
Conclusions :
In SIRT5 deficient mice, the decrease of tear secretion and the accumulation of the lipid droplet were confirmed, the possibility that the metabolism change of the fatty acid including the HMG-CoA was suggested.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.