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An Analysis of Metabolic Changes in the Retina and Retinal Pigment Epithelium of Aging Mice
Authors:Kristine A. Tsantilas  Whitney M. Cleghorn  Celia M. Bisbach  Jeremy A. Whitson  Daniel T. Hass  Brian M. Robbings  Martin Sadilek  Jonathan D. Linton  Austin M. Rountree  Ana P. Valencia  Mariya T. Sweetwyne  Matthew D. Campbell  Huiliang Zhang  Connor S. R. Jankowski  Ian R. Sweet  David J. Marcinek  Peter S. Rabinovitch  James B. Hurley
Abstract:PurposeThe purpose of this study was to present our hypothesis that aging alters metabolic function in ocular tissues. We tested the hypothesis by measuring metabolism in aged murine tissues alongside retinal responses to light.MethodsScotopic and photopic electroretinogram (ERG) responses in young (3–6 months) and aged (23–26 months) C57Bl/6J mice were recorded. Metabolic flux in retina and eyecup explants was quantified using U-13C-glucose or U-13C-glutamine with gas chromatography-mass spectrometry (GC-MS), O2 consumption rate (OCR) in a perifusion apparatus, and quantifying adenosine triphosphatase (ATP) with a bioluminescence assay.ResultsScotopic and photopic ERG responses were reduced in aged mice. Glucose metabolism, glutamine metabolism, OCR, and ATP pools in retinal explants were mostly unaffected in aged mice. In eyecups, glutamine usage in the Krebs Cycle decreased while glucose metabolism, OCR, and ATP pools remained stable.ConclusionsOur examination of metabolism showed negligible impact of age on retina and an impairment of glutamine anaplerosis in eyecups. The metabolic stability of these tissues ex vivo suggests age-related metabolic alterations may not be intrinsic. Future experiments should focus on determining whether external factors including nutrient supply, oxygen availability, or structural changes influence ocular metabolism in vivo.
Keywords:aging   retina   retinal pigment epithelium   metabolism   electroretinogram
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