"Energetics of the outer retina II: Calculation of a spatio-temporal energy budget in retinal pigment epithelium and photoreceptor cells based on quantification of cellular processes".

Christina Kiel, Stella Prins, Alexander J E Foss, Philip J Luthert
Author Information
  1. Christina Kiel: Department of Molecular Medicine, University of Pavia, Pavia, Italy. ORCID
  2. Stella Prins: UCL Institute of Ophthalmology, University College London, London, United Kingdom.
  3. Alexander J E Foss: Department of Ophthalmology, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom.
  4. Philip J Luthert: UCL Institute of Ophthalmology, University College London, London, United Kingdom.

Abstract

The outer retina (OR) is highly energy demanding. Impaired energy metabolism combined with high demands are expected to cause energy insufficiencies that make the OR susceptible to complex blinding diseases such as age-related macular degeneration (AMD). Here, anatomical, physiological and quantitative molecular data were used to calculate the ATP expenditure of the main energy-consuming processes in three cell types of the OR for the night and two different periods during the day. The predicted energy demands in a rod dominated (perifovea) area are 1.69 x 1013 ATP/s/mm2 tissue in the night and 6.53 x 1012 ATP/s/mm2 tissue during the day with indoor light conditions. For a cone-dominated foveal area the predicted energy demands are 6.41 x 1012 ATP/s/mm2 tissue in the night and 6.75 x 1012 ATP/s/mm2 tissue with indoor light conditions during daytime. We propose the likely need for diurnal/circadian shifts in energy demands to efficiently stagger all energy consuming processes. Our data provide insights into vulnerabilities in the aging OR and suggest that diurnal constraints may be important when considering therapeutic interventions to optimize metabolism.

References

  1. Biochim Biophys Acta. 2010 Jun;1803(6):673-83 [PMID: 19879902]
  2. Biosci Rep. 2022 Sep 30;42(9): [PMID: 36043949]
  3. J Biol Chem. 1966 Dec 25;241(24):5936-40 [PMID: 5954370]
  4. Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12871-6 [PMID: 14566050]
  5. EMBO J. 2019 Sep 16;38(18):e100811 [PMID: 31436334]
  6. Sci Rep. 2017 Aug 24;7(1):9296 [PMID: 28839191]
  7. Methods Enzymol. 2009;455:157-92 [PMID: 19289206]
  8. Curr Biol. 2021 May 24;31(10):R619-R632 [PMID: 34033794]
  9. Proc Natl Acad Sci U S A. 2022 May 10;119(19):e2117553119 [PMID: 35522714]
  10. J Neurosci. 2003 Jan 1;23(1):1-6 [PMID: 12514193]
  11. Eur J Biochem. 1986 May 2;156(3):677-84 [PMID: 3699030]
  12. Int J Mol Sci. 2020 Nov 09;21(21): [PMID: 33182490]
  13. Integr Med (Encinitas). 2014 Apr;13(2):8-15 [PMID: 26770084]
  14. Cell Rep. 2015 Dec 1;13(9):1868-80 [PMID: 26655902]
  15. Eye Brain. 2010;2:99-116 [PMID: 23226947]
  16. J Biol Chem. 1967 May 25;242(10):2389-96 [PMID: 4381697]
  17. Biochem J. 1962 Jan;82:205-12 [PMID: 14006661]
  18. Cell. 2009 Apr 17;137(2):356-68 [PMID: 19379699]
  19. iScience. 2023 Jan 05;26(2):105931 [PMID: 36711246]
  20. PLoS One. 2024 Dec 31;19(12):e0312260 [PMID: 39739933]
  21. Bioessays. 2013 Dec;35(12):1050-5 [PMID: 24114984]
  22. Eye (Lond). 1992;6 ( Pt 2):136-44 [PMID: 1624035]
  23. Metab Eng. 2020 Sep;61:288-300 [PMID: 32619503]
  24. Biophys Rev. 2015 Sep;7(3):269-299 [PMID: 28510227]
  25. Am J Ophthalmol. 1996 Feb;121(2):181-9 [PMID: 8623888]
  26. Vision Res. 2007 Oct;47(22):2901-11 [PMID: 17320143]
  27. Channels (Austin). 2013 Nov-Dec;7(6):426-31 [PMID: 24037064]
  28. Elife. 2020 Sep 17;9: [PMID: 32940604]
  29. Adv Exp Med Biol. 2023;1415:435-441 [PMID: 37440069]
  30. Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2312-5 [PMID: 12598655]
  31. Cancer Res. 1999 Jun 1;59(11):2522-6 [PMID: 10363965]
  32. Graefes Arch Clin Exp Ophthalmol. 1992;230(6):505-10 [PMID: 1427131]
  33. Cell. 2016 Apr 21;165(3):535-50 [PMID: 27104977]
  34. Curr Opin Cell Biol. 1999 Aug;11(4):466-75 [PMID: 10449335]
  35. Front Immunol. 2020 Nov 13;11:604205 [PMID: 33281830]
  36. PLoS Comput Biol. 2006 Dec 1;2(12):e172 [PMID: 17140284]
  37. Annu Rev Vis Sci. 2021 Sep 15;7:665-692 [PMID: 34102066]
  38. EMBO J. 2019 Jul 1;38(13):e101414 [PMID: 31268607]
  39. Ophthalmology. 1995 Dec;102(12):1853-9 [PMID: 9098287]
  40. Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2864-7 [PMID: 19164551]
  41. Proc Natl Acad Sci U S A. 2019 Nov 26;116(48):24100-24107 [PMID: 31712411]
  42. Biochim Biophys Acta Mol Cell Res. 2018 Jul 17;1865(10):1397-1409 [PMID: 30021127]
  43. Vis Neurosci. 2002 Jul-Aug;19(4):395-407 [PMID: 12511073]
  44. J Cell Sci. 2021 Feb 8;134(3): [PMID: 33558441]
  45. J Neurochem. 1983 Oct;41(4):942-9 [PMID: 6555219]
  46. Trends Cell Biol. 2020 Feb;30(2):157-167 [PMID: 31836280]
  47. Int J Mol Sci. 2019 Jul 22;20(14): [PMID: 31336621]
  48. J Comp Neurol. 1990 Feb 22;292(4):497-523 [PMID: 2324310]
  49. J R Soc Interface. 2020 Feb;17(163):20190735 [PMID: 32019471]
  50. Proc Natl Acad Sci U S A. 2020 Aug 11;117(32):19599-19603 [PMID: 32719136]
  51. J Biol Chem. 1958 Apr;231(2):751-64 [PMID: 13539009]
  52. Vision Res. 1998 Sep;38(17):2539-49 [PMID: 12116702]
  53. Exp Eye Res. 2006 Feb;82(2):351-3 [PMID: 16337628]
  54. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4533-7 [PMID: 2352934]
  55. Nat Rev Mol Cell Biol. 2009 Sep;10(9):623-35 [PMID: 19672277]
  56. Invest Ophthalmol Vis Sci. 1999 Feb;40(2):443-9 [PMID: 9950604]
  57. Curr Biol. 2008 Dec 23;18(24):1917-21 [PMID: 19084410]
  58. Biophys J. 1970 May;10(5):380-412 [PMID: 5439318]
  59. Netw Syst Med. 2020 Aug 03;3(1):105-121 [PMID: 32789304]
  60. BMC Biol. 2023 Apr 17;21(1):84 [PMID: 37069561]
  61. Nature. 2011 May 19;473(7347):337-42 [PMID: 21593866]
  62. Front Genet. 2015 Jan 26;6:2 [PMID: 25674102]
  63. Proc Natl Acad Sci U S A. 2021 Jun 29;118(26): [PMID: 34140336]
  64. J Cell Biol. 2016 Oct 10;215(1):15-25 [PMID: 27738003]
  65. Invest Ophthalmol Vis Sci. 2019 Jul 1;60(8):2848-2859 [PMID: 31260035]
  66. Mol Cell Neurosci. 2022 Dec;123:103793 [PMID: 36396040]
  67. Elife. 2021 Jan 29;10: [PMID: 33512317]
  68. Vision Res. 2012 Dec 15;75:5-10 [PMID: 22892112]
  69. Nature. 1993 Apr 22;362(6422):709-15 [PMID: 8469282]

MeSH Term

Energy Metabolism
Retinal Pigment Epithelium
Humans
Adenosine Triphosphate
Retina
Circadian Rhythm
Retinal Cone Photoreceptor Cells
Photoreceptor Cells
Male
Macular Degeneration

Chemicals

Adenosine Triphosphate

Word Cloud

Created with Highcharts 10.0.0energyORdemandsxATP/s/mm2tissuenight61012outerretinametabolismdataprocessesdaypredictedareaindoorlightconditionshighlydemandingImpairedcombinedhighexpectedcauseinsufficienciesmakesusceptiblecomplexblindingdiseasesage-relatedmaculardegenerationAMDanatomicalphysiologicalquantitativemolecularusedcalculateATPexpendituremainenergy-consumingthreecelltypestwodifferentperiodsroddominatedperifovea169101353cone-dominatedfoveal4175daytimeproposelikelyneeddiurnal/circadianshiftsefficientlystaggerconsumingprovideinsightsvulnerabilitiesagingsuggestdiurnalconstraintsmayimportantconsideringtherapeuticinterventionsoptimize"EnergeticsII:Calculationspatio-temporalbudgetretinalpigmentepitheliumphotoreceptorcellsbasedquantificationcellularprocesses"

Similar Articles

Cited By

No available data.