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Lucia Podracka, Katja Vehanen, Timo Tuulos, Seppo Ronkko, Kai Kaarniranta, Hannu Uusitalo, Giedrius Kalesnykas; BDNF-deficiency Downregulates SIRT1 and Upregulates SIRT2 Expression in Aging Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2697.
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Sirtuins (silent information regulators) are a group of deacetylase enzymes that are involved in a variety of cellular functions, including stress response, DNA repair, neuronal survival, and axonal degeneration. However, their expression levels in retina during aging have not been explored to date. In the present study, we aimed to compare SIRT1 and SIRT2 expression in retinas of mice that lack brain derived neurotrophic factor (BDNF+/-) and their wild type littermates (WT) at young and old age.
Eyes from 2- and 22-months old WT and BDNF+/- mice (The Jackson Laboratory, Bar Harbor, ME, USA) were used. SIRT1 and SIRT2 protein levels in retina were determined by Western blotting. Paraffin-embedded retinal sections were immunostained for SIRT1 and SIRT2 using diaminobenzidine (DAB) to determine their localisation and abundance in various retinal layers. The presence of SIRT1 and SIRT2 in retinal ganglion cells (RGCs) was studied in more detail.
Western blot analysis of the whole retina showed that SIRT1 expression is upregulated in 22-month old WT mice and downregulated in 22-month old BDNF+/- mice when compared to 2-month old groups. Immunohistochemistry of RGC layer confirmed downregulation of SIRT1 in both, WT and BDNF+/- 22-months old mice compared to 2-month old. In contrast, levels of SIRT2 increased with aging, in both, WT and BDNF+/- mice. The expression of SIRT2, but not SIRT1, was more prominent in BDNF-deficient mice compared to WT at both age groups.
Our results postulate that BDNF deficiency in aging retina is accompanied by a decrease in neuroprotective SIRT1 and an increase in SIRT2 which has been implicated to promote neuronal death. These effects could be linked to age-related neurodegenerative conditions and could be a potential target for drug development.
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