Tsantilas Kristine A, Cleghorn Whitney M, Bisbach Celia M, Whitson Jeremy A, Hass Daniel T, Robbings Brian M, Sadilek Martin, Linton Jonathan D, Rountree Austin M, Valencia Ana P, Sweetwyne Mariya T, Campbell Matthew D, Zhang Huiliang, Jankowski Connor S R, Sweet Ian R, Marcinek David J, Rabinovitch Peter S, Hurley James B
Department of Biochemistry, University of Washington, Seattle, Washington, United States.
Department of Biology, Davidson College, Davidson, North Carolina, United States.
Invest Ophthalmol Vis Sci. 2021 Nov 1;62(14):20. doi: 10.1167/iovs.62.14.20.
The 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.
Scotopic 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.
Scotopic 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.
Our 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.
本研究的目的是提出我们的假设，即衰老会改变眼组织的代谢功能。我们通过测量老年小鼠组织的代谢以及视网膜对光的反应来验证这一假设。
记录年轻（3 - 6个月）和老年（23 - 26个月）C57Bl/6J小鼠的暗视和明视视网膜电图（ERG）反应。使用U - 13C - 葡萄糖或U - 13C - 谷氨酰胺通过气相色谱 - 质谱联用仪（GC - MS）对视网膜和眼球外植体的代谢通量进行定量，使用灌注装置测量氧消耗率（OCR），并通过生物发光测定法定量三磷酸腺苷（ATP）。
老年小鼠的暗视和明视ERG反应降低。老年小鼠视网膜外植体中的葡萄糖代谢、谷氨酰胺代谢、OCR和ATP池大多未受影响。在眼球中，三羧酸循环中的谷氨酰胺利用减少，而葡萄糖代谢、OCR和ATP池保持稳定。
我们对代谢的研究表明，年龄对视网膜的影响可忽略不计，而眼球中谷氨酰胺补充途径受损。这些组织在体外的代谢稳定性表明，与年龄相关的代谢改变可能不是内在的。未来的实验应集中于确定包括营养供应、氧气供应或结构变化在内的外部因素是否会影响体内眼代谢。
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