Histone deacetylase SIRT6 participates in early neurodegenerative events in diabetic retinopathy

EMILIA SOLEDAD BOGNI; ADA YESTE; FRANCISCO QUINTANA; RAUL MOSTOSLAVSKY

Mar del Plata

Congreso; Reunión Conjunta SAIC-SAI-SAFE; 2016

Diabetic retinopathy(DR) is the leading cause of blindness worldwide. Recent research has demonstrated that DR is not only a microvascular disease but may be a result of neurodegenerative processes. Current investigation points to the role of histone acetyl transferases and deacetylasesas regulators of key genes linked to diabetes. SIRT6, a NAD-dependentdeacylase, modulates aging, cancer, energy metabolism, neurodegeneration and DNA repair. In previous studies we showed that SIRT6 deficiency causes major retinal transmission defects related to changes in expression of glycolytic genes and glutamate receptors, as well as elevated levels of apoptosis in inner retina cells. Given the importance of glucose availability for retina function and the critical role for SIRT6 in modulating glycolysis, the main goal of this work was to analyze SIRT6 involvement in the molecular machinery that regulates the development of experimental DR. Using the non-obese diabetic (NOD) mouse strain that spontaneously develops type 1 Diabetes, we determined by Western blot and RT-PCR that high glucose concentrations (>200mg/dl) induced increased VEGF (p