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bioRxiv · 10.1101/2021.04.06.438698

Metabolic function in aging retina and retinal pigment epithelium remains robust despite vision loss

Tsantilas, K. A.·Cleghorn, W. M.·Bisbach, C. M.·Whitson, J. A.·Hass, D. T.·Robbings, B. M.·Sadilek, M.·Linton, J. D.·Rountree, A. M.·Valencia, A. P.·Sweetwyne, M. T.·Campbell, M. D.·Zhang, H.·Jankowski, C. S. R.·Sweet, I. R.·Marcinek, D. J.·Rabinovitch, P. S.·Hurley, J. B.
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Abstract

PurposeCharacterize how metabolic function in the murine retina and retinal pigment epithelium-choroid-sclera (eyecup) complex is impacted by natural aging. MethodsWe examined scotopic and photopic visual function of young (3-6 months) and aged (23-26 months) C57Bl/6J mice using electroretinograms (ERGs). Metabolic changes in retina and eyecup explants were characterized by measuring uptake and usage of U-13C-glucose or U-13C-glutamine at different timepoints by gas chromatography-mass spectrometry (GC-MS), measuring oxygen consumption rate (OCR) using a perifusion apparatus, and determining ATP levels with a bioluminescence assay. ResultsScotopic and photopic ERG responses declined in aged mice. Glucose metabolism, glutamine metabolism, OCR, and ATP pools in retinal explants were mostly unaffected by the age of the mouse. In eyecups, glutamine usage in the Krebs Cycle decreased while glucose metabolism, OCR, and ATP pools remained stable. ConclusionsThe ex vivo approach in our study to examine aging glucose and glutamine metabolism in retina and RPE showed negligible impact of age on retina and an impairment of glutamine anaplerosis in eyecups. The surprising metabolic stability of these tissues ex vivo suggests age-related metabolic alterations in these tissues may not be intrinsic. Future experiments should focus on determining whether external factors including nutrient supply, oxygen availability, or other structural changes influence ocular metabolism in vivo.

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Tsantilas, K. A., Cleghorn, W. M., Bisbach, C. M., Whitson, J. A., Hass, D. T., Robbings, B. M., Sadilek, M., Linton, J. D., Rountree, A. M., Valencia, A. P., Sweetwyne, M. T., Campbell, M. D., Zhang, H., Jankowski, C. S. R., Sweet, I. R., Marcinek, D. J., Rabinovitch, P. S., Hurley, J. B.. 2021-04-06. Metabolic function in aging retina and retinal pigment epithelium remains robust despite vision loss. https://doi.org/10.1101/2021.04.06.438698

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