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Motoshi Hayano, Hayato Nagashima, Sachie Amano, Atsushi Sakuma, Takako Hishiki, Makoto Suematsu, Kazuo Tsubota; Maintenance of tissue stiffness via metabolism in Presbyopia. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2096. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The tissue stiffness is decreased with age not only in lens but also in liver, heart and brain causing aging related diseases such as presbyopia, cirrhosis, myocardial infarction and Alzheimer diseases. The accommodative ability of eye requires for clear vision at near and loss of the ability leads to presbyopia. Although the transparency and lens stiffness are maintained by protein function and metabolism in lens, it remains unknown the molecular mechanisms regulating the accommodative ability of eye with age. In this study, we have tested metabolome analysis in young and aged mice and rat to understand whether metabolism contributes the maintenance of tissue stiffness and induction of diseases.
Metabolite analysis in lenses, capillary electrophoresis-mass spectrometry (CE/MS) (Agilent 6530 Q-TOF) evaluating 144 metabolites was used in mouse and rat (n=6and 9; young and aged mice, n=6 and 4; young and aged rats). The concentration of metabolites was compared by student T tests and p value < 0.05 was considered to be significant. In addition, the proteins related to significant pathway were detected by western blotting analysis.
Metabolite analysis showed that amino acids such as Glu, Asp and Ala are decreased with age in both mice and rat during aging. In addition, TCA-cycle and methylated product pathway are significantly changed with age. Interestingly, glutathione known to be contained in lens with high concentration to maintain lens transparency was not changed in mice and rat although lens stiffness is decreased. Metabolome and protein analysis suggested that metabolome reprogramming such as energy pathway has a crucial role for maintenance of lens stiffness and presbyopia.
Our data showed that metabolisms including energy pathway were changed along with lens hardening during aging. The changes in metabolism was conserved between mice and rat indicating metabolome reprogramming alters tissue stiffness. Glycolysis, lipid biogenesis and mitochondria function are associated with inflammation, cell proliferation, DNA damage response and differentiation. The maintenance of tissue stiffness could be an novel aging marker and epithelial cells (LECs) may have a crucial role for lens metabolism and presbyopia.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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