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X. Koufomichali, N. M. Krah, G. Trichonas, A. Manola, A. Thanos, Y. Morizane, E. Gragoudas, D. Vavvas; The Role of AMP-Dependent Kinase a1 Isoform (AMPKa1) in Retinopathy of Prematurity. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4462.
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Retinopathy of Prematurity (ROP) is a retinal vasoproliferative disease, which, despite the recent advancement in treatment, remains among the leading causes of visual impairment in childhood that will lead to a lifetime of incapacity. 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 HIF1a, VEGF and eNOS; molecules important in ROP pathogenesis. We study the role of AMPK in this angiogenic disease by examining the effect of its absence in the model of Oxygen Induced Retinopathy (OIR).
Seven days after birth (postnatal day 7, P7), litters of a1 isoform KO (AMPKa1-/-) and WT 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. On P17 and under deep anesthesia, eyes were enucleated, retinas were isolated and stained for Isolectin B4-FITC.The retinas were whole-mounted and quantification of retinal vaso-obliteration and neovascularization was performed.
In two independent experiments, whole-mount analysis in WT and a1 isoform KO mice revealed a 30% to 130% more vaso-obliteration in the a1 knockout mice (p<0.05) but no statistically significant difference in neovascularization.
AMPKa1 does not appear to be a major factor in the pathogenesis of oxygen induced retinopathy. Further investigation will be contacted with the use of CNS specific double a1/a2 isoform KO mice.
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