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Lei Xu, John Ash; AMPKα2 plays a unique role in Cone function and survival. Invest. Ophthalmol. Vis. Sci. 2016;57(12):177.
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© 2017 Association for Research in Vision and Ophthalmology.
Retinal neurons have a high-energy demand, but have a poor energy storage capacity suggesting the importance of tight regulation of metabolism. AMP-activated protein kinase (AMPK) is thought to be a master regulator of metabolic regulation. AMPKα1 and AMPKα2 are two independent isoforms of the catalytic alpha (α) subunit. The goal of this study is to determine whether deletion of AMPKα1 or AMPKα2 affects function of survival or retinal photoreceptors.
Chx10-Cre;AMPKα1f/f, Chx10-Cre;AMPKα2 f/f, and double knockout mice were examined at various ages. Retinal function was measured by electroretinography (ERG) and retinal structure was observed by Spectral domain Optical Coherence Tomography (SD-OCT). Western blots and real time PCR were used to study opsin expression. Immunohistochemistry (IHC) was used to count cone photoreceptors and measure opsin and arrestin co-localization. All procedures with animals were conducted in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.
All conditional knockout mice have normal retinal structure, thickness and scotopic ERG a-wave amplitudes at 3 months of age. AMPKα1 knockout mice have normal cone function at 3 and 6 months. However, AMPKα2 and double knockout mice have decreased photopic ERG responses as early as 2 months of age. IHC using cone arrestin, M-opsin and S-opsin antibodies in retinal sections shows reduced arrestin and opsin expression. Additionally, we found that there is a reduction in cone number at 3 months of age relative to Cre negative control mice.
Our data showing that reduced cone function, reduced cone numbers, and reduced expression of opsin and arrestin in surviving cones in retinal knockout mice suggest that AMPKα2 is an essential protein in cones. The data also show that AMPKα1 cannot compensate for the loss of AMPKα2, since double knockout mice have a similar phenotype to the AMPKα2 single knockout. Overall, those data demonstrated that AMPKα2 but not α1 has a unique role in cones.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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