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X. Koufomichali, Y. Morizane, A. Manola, A. Thanos, G. Trichonas, E. Gragoudas, J. W. Miller, D. Vavvas; The Role of AMP-Dependent Kinase (AMPK) in Retinopathy of Prematurity. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3122.
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© ARVO (1962-2015); The Authors (2016-present)
Retinopathy of prematurity (ROP) is a major cause of childhood blindness. It features cessation of vessel growth that leads to a stressed, hypoxic peripheral retina and subsequent retinal neovascularization. Increased energy expenditure and decreased energy supply depletes ATP and increases AMP levels leading to activation of the energy sensor protein AMP-dependent kinase (AMPK). Previously it has been shown that AMPK activation leads to increased levels of HIF1, VEGF and eNOS; molecules important in ROP pathogenesis. We study the role of AMPK in this angiogenic disease by examining its activity in the model of Oxygen Induced Retinopathy (OIR).
Seven days after birth (postnatal day 7, P7), litters of wild type C57BL/6J mice were exposed to 75% oxygen for 5 days until P12. Immediately after exposure, they were transferred to room air for 5 days until P17. The control litters remained at room air. After deep anesthesia, eyes were enucleated and put in chilled PBS. Dissection of retina was performed in chilled PBS under dissecting microscope. Standard lysis buffer was used to lyse and homogenize the retina followed by SDS-PAGE gels and Western blotting. Activated Acetyl-CoA Carboxylase (pACC) -downstream effector of AMPK- and activated AMPK were investigated in days P10, P12 and P15.
Upon return to room air (P12) activity of AMPK in retinas of oxygen-exposed mice was significantly elevated compared to control animals (139%, p<0.05). On P15, three days after return to normal oxygen levels, activity of AMPK decreased to levels below the control animals (71%, p<0.05).
AMP-dependent kinase activity is significantly elevated upon return to room air in the oxygen-exposed group and precedes pathologic neovascularization. More experiments are needed to investigate the role of AMPK in ROP and its potential as a novel therapeutic target. In addition, severity of OIR in wild type versus knockout mice for the two catalytic isoforms of AMPK, a2 and a1, is under investigation.
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