“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”
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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 10 13 ATP/s/mm 2 tissue in the night and 6.53 x 10 12 ATP/s/mm 2 tissue during the day with indoor light conditions. For a cone-dominated foveal area the predicted energy demands are 6.41 x 10 12 ATP/s/mm 2 tissue in the night and 6.75 x 10 12 ATP/s/mm 2 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.
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Cites
Global quantification of mammalian gene expression control
Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566 · see citing works
Instability and decay of the primary structure of DNA
Lindahl, T. (1993) · Nature · doi:10.1038/362709a0 · Cited by 5,679 · see citing works
On the Dependency of Cellular Protein Levels on mRNA Abundance
Liu, Y., Beyer, A., & Aebersold, R. (2016) · Cell · doi:10.1016/j.cell.2016.03.014 · Cited by 3,221 · see citing works
Human photoreceptor topography
Curcio, C. A., Sloan, K. R., Kalina, R. E., & Hendrickson, A. E. (1990) · The Journal of Comparative Neurology · doi:10.1002/cne.902920402 · Cited by 2,792 · see citing works
Lysosome biogenesis and lysosomal membrane proteins: trafficking meets function
Säftig, P., & Klumperman, J. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2745 · Cited by 1,702 · see citing works
Oxidative damage to DNA during aging: 8-hydroxy-2'-deoxyguanosine in rat organ DNA and urine.
Fraga, C. G., Shigenaga, M. K., Park, J. W., Degan, P., & Ames, B. N. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.12.4533 · Cited by 1,106 · see citing works
Non-coding RNA: what is functional and what is junk?
Palazzo, A. F., & Lee, E. S. (2015) · Frontiers in Genetics · doi:10.3389/fgene.2015.00002 · Cited by 891 · see citing works
Nuclear Architecture of Rod Photoreceptor Cells Adapts to Vision in Mammalian Evolution
Solovei, I. V., Kreysing, M., Lanctôt, C., Kösem, S., Peichl, L., Cremer, T. J., Guck, J. R., & Joffe, B. I. (2009) · Cell · doi:10.1016/j.cell.2009.01.052 · Cited by 785 · see citing works
Endogenous DNA double-strand breaks: production, fidelity of repair, and induction of cancer
Vilenchik, M. M., & Knudson, A. G. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2135498100 · Cited by 717 · see citing works
Milo, R. (2013) · BioEssays · doi:10.1002/bies.201300066 · Cited by 643 · see citing works
Dark Current and Photocurrent in Retinal Rods
Hagins, W. A., Penn, R. D., & Yoshikami, S. (1970) · Biophysical Journal · doi:10.1016/s0006-3495(70)86308-1 · Cited by 562 · see citing works
The role of ARF and Rab GTPases in membrane transport
Chavrier, P., & Goud, B. (1999) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(99)80067-2 · Cited by 496 · see citing works
Kressler, D., Hurt, E., & Baßler, J. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2009.10.009 · Cited by 492 · see citing works
Turnover of Constituents of the Endoplasmic Reticulum Membranes of Rat Hepatocytes
Omura, T., Siekevitz, P., & Palade, G. E. (1967) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)95974-0 · Cited by 482 · see citing works
Energy metabolism of the visual system
Wong‐Riley, M. T. T. (2010) · Eye and Brain · doi:10.2147/eb.s9078 · Cited by 456 · see citing works
ATP Consumption by Mammalian Rod Photoreceptors in Darkness and in Light
Okawa, H., Sampath, A. P., Laughlin, S. B., & Fain, G. (2008) · Current Biology · doi:10.1016/j.cub.2008.10.029 · Cited by 404 · see citing works
DNA damage-how and why we age?
Yousefzadeh, M., Henpita, C., Vyas, R., Soto-Palma, C., Robbins, P., & Niedernhofer, L. (2021) · eLife · doi:10.7554/elife.62852 · Cited by 399 · see citing works
Voigt, A. P., Mulfaul, K., Mullin, N. K., Flamme‐Wiese, M. J., Giacalone, J. C., Stone, E. M., Tucker, B. A., Scheetz, T. E., & Mullins, R. F. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1914143116 · Cited by 375 · see citing works
Endogenous apurinic/apyrimidinic sites in genomic DNA of mammalian tissues.
Nakamura, J., & Swenberg, J. A. (1999) · PubMed · Cited by 356 · see citing works
A single‐cell transcriptome atlas of the adult human retina
Lukowski, S. W., Lo, C. Y.-W., Sharov, A. A., Nguyen, Q. H., Fang, L., Hung, S. S. C., Zhu, L., Zhang, T., Grünert, U., Nguyen, T., et al. (2019) · The EMBO Journal · doi:10.15252/embj.2018100811 · Cited by 347 · see citing works
Actin-ATP Hydrolysis Is a Major Energy Drain for Neurons
Bernstein, B. W., & Bamburg, J. R. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-01-00002.2003 · Cited by 293 · see citing works
Hoang, Q. V., Linsenmeier, R. A., Chung, C., & Curcio, C. A. (2002) · Visual Neuroscience · doi:10.1017/s0952523802194028 · Cited by 285 · see citing works
Drasdo, N., Millican, C. L., Katholi, C. R., & Curcio, C. A. (2007) · Vision Research · doi:10.1016/j.visres.2007.01.007 · Cited by 283 · see citing works
The cytoskeleton in phagocytosis and macropinocytosis
Mylvaganam, S., Freeman, S. A., & Grinstein, S. (2021) · Current Biology · doi:10.1016/j.cub.2021.01.036 · Cited by 263 · see citing works
Count and density of human retinal photoreceptors
Jonas, J. B., Schneider, U., & Naumann, G. O. H. (1992) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/bf00181769 · Cited by 252 · see citing works
Retinal Pigment Epithelial Cell Count, Distribution, and Correlations in Normal Human Eyes
Panda‐Jonas, S., Jonas, J. B., & Jakobczyk-Zmija, M. J. (1996) · American Journal of Ophthalmology · doi:10.1016/s0002-9394(14)70583-5 · Cited by 244 · see citing works
Turnover of Liver Ribosomes in Fed and in Fasted Rats
Hirsch, C. A., & Hiatt, H. H. (1966) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)96360-x · Cited by 219 · see citing works
Retinal photoreceptor density decreases with age
Panda-Jonas, S., Jonas, J. B., & Jakobczyk-Zmija, M. (1995) · Ophthalmology · doi:10.1016/s0161-6420(95)30784-1 · Cited by 208 · see citing works
MEASUREMENT OF PROTEIN TURNOVER IN RAT LIVER
Swick, R. W. (1958) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)70439-0 · Cited by 206 · see citing works
Circadian oscillation of nucleotide excision repair in mammalian brain
Kang, T., Reardon, J. T., Kemp, M. G., & Sancar, A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812638106 · Cited by 205 · see citing works
Retina Metabolism and Metabolism in the Pigmented Epithelium: A Busy Intersection
Hurley, J. B. (2021) · Annual Review of Vision Science · doi:10.1146/annurev-vision-100419-115156 · Cited by 196 · see citing works
The dependence of the respiration of brain cortex on active cation transport
Whittam, R. (1962) · Biochemical Journal · doi:10.1042/bj0820205 · Cited by 193 · see citing works
Evidence for rotation of V 1 -ATPase
Imamura, H., Nakano, M., Noji, H., Muneyuki, E., Ohkuma, S., Yoshida, M., & Yokoyama, K. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0436796100 · Cited by 187 · see citing works
The relationships of age changes in retinal pigment epithelium and Bruch's membrane.
Okubo, A., Rosa, R. H., Bunce, C., Alexander, R., Fan, J. T., Bird, A. C., & Luthert, P. J. (1999) · PubMed · Cited by 172 · see citing works
Self-citationThe circadian coordination of cell biology
Chaix, A., Zarrinpar, A., & Panda, S. (2016) · Journal of Cell Biology · doi:10.1083/jcb.201603076 · Cited by 159 · see citing works
Phagocytosis by the Retinal Pigment Epithelium: Recognition, Resolution, Recycling
Kwon, W., & Freeman, S. A. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.604205 · Cited by 157 · see citing works
A morphological comparison of foveal development in man and monkey
Hendrickson, A. E. (1992) · Eye · doi:10.1038/eye.1992.29 · Cited by 156 · see citing works
Fueling the cytoskeleton – links between cell metabolism and actin remodeling
DeWane, G., Salvi, A. M., & DeMali, K. A. (2021) · Journal of Cell Science · doi:10.1242/jcs.248385 · Cited by 148 · see citing works
Chapter 6 Kinetic and Equilibrium Analysis of the Myosin ATPase
Cruz, E. M. D. L., & Ostap, E. M. (2009) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(08)04206-7 · Cited by 141 · see citing works
Physical bioenergetics: Energy fluxes, budgets, and constraints in cells
Yang, X., Heinemann, M., Howard, J., Huber, G., Iyer‐Biswas, S., Treut, G. L., Lynch, M., Montooth, K. L., Needleman, D. J., Simone Pigolotti, A., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2026786118 · Cited by 128 · see citing works
Elevated energy requirement of cone photoreceptors
Ingram, N. T., Fain, G., & Sampath, A. P. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2001776117 · Cited by 115 · see citing works
Ortolan, D., Sharma, R., Volkov, A. I., Maminishkis, A., Hotaling, N. A., Huryn, L. A., Cukras, C. A., Marco, S. D., Bisti, S., & Bharti, K. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2117553119 · Cited by 101 · see citing works
Daniel, J. L., Molish, I. R., Robkin, L., & Holmsen, H. (1986) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1986.tb09631.x · Cited by 91 · see citing works
Tarau, I., Berlin, A., Curcio, C. A., & Ach, T. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20143578 · Cited by 89 · see citing works
What CHO is made of: Variations in the biomass composition of Chinese hamster ovary cell lines
Széliová, D., Ruckerbauer, D. E., Galleguillos, S. N., Petersen, L. B., Natter, K., Hanscho, M., Troyer, C., Causon, T. J., Schoeny, H., Christensen, H. B., et al. (2020) · Metabolic Engineering · doi:10.1016/j.ymben.2020.06.002 · Cited by 78 · see citing works
Rab and Arf proteins at the crossroad between membrane transport and cytoskeleton dynamics
Kjos, I., Vestre, K., Guadagno, N. A., Distefano, M. B., & Progida, C. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2018.07.009 · Cited by 64 · see citing works
Topography of Neurons in the Rod Pathway of Human Retina
Lee, S., Martin, P. R., & Grünert, U. (2019) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.19-27217 · Cited by 60 · see citing works
Functional architecture of primate cone and rod axons
Hsu, A., Tsukamoto, Y., Smith, R. G., & Sterling, P. (1998) · Vision Research · doi:10.1016/s0042-6989(97)00370-2 · Cited by 59 · see citing works
Cycling Transcriptional Networks Optimize Energy Utilization on a Genome Scale
Wang, G.-Z., Hickey, S. L., Shi, L., Huang, H.-C., Nakashe, P., Koike, N., Tu, B. P., Takahashi, J. S., & Konopka, G. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.10.043 · Cited by 58 · see citing works
Computational Model Explains High Activity and Rapid Cycling of Rho GTPases within Protein Complexes
Goryachev, A. B., & Pokhilko, A. V. (2006) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0020172 · Cited by 56 · see citing works
Squeezing in a Meal: Myosin Functions in Phagocytosis
Barger, S. R., Gauthier, N. C., & Krendel, M. (2019) · Trends in Cell Biology · doi:10.1016/j.tcb.2019.11.002 · Cited by 49 · see citing works
Maddox, J. W., Randall, K., Yadav, R. P., Williams, B., Hagen, J., Derr, P. J., Kerov, V., Santina, L. D., Baker, S. A., Artemyev, N. O., et al. (2020) · eLife · doi:10.7554/elife.62184 · Cited by 46 · see citing works
Molecular assemblies that control rhodopsin transport to the cilia
Deretic, D., & Wang, J. (2012) · Vision Research · doi:10.1016/j.visres.2012.07.015 · Cited by 44 · see citing works
Different Rates of Synthesis and Turnover of Ribosomal RNA in Rat Brain and Liver
Stoykova, A., Dudov, K. P., Dabeva, M. D., & Hadjiolov, A. A. (1983) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1983.tb09038.x · Cited by 39 · see citing works
Mitochondria-Fundamental to Life and Health.
Pizzorno, J. E. (2014) · PubMed Central · Cited by 39 · see citing works
Kinesin Motor Enzymology: Chemistry, Structure, and Physics of Nanoscale Molecular Machines
Cochran, J. C. (2015) · Biophysical Reviews · doi:10.1007/s12551-014-0150-6 · Cited by 38 · see citing works
Fluid and solute transport across the retinal pigment epithelium: a theoretical model
Dvoriashyna, M., Foss, A. J. E., Gaffney, E. A., & Repetto, R. (2020) · Journal of The Royal Society Interface · doi:10.1098/rsif.2019.0735 · Cited by 33 · see citing works
Self-citationLoss of Tmem30a leads to photoreceptor degeneration
Zhang, L., Yang, Y., Li, S., Zhang, S., Zhu, X., Tai, Z., Yang, M., Liu, Y., Guo, X., Chen, B., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-09506-5 · Cited by 28 · see citing works
Kinesin-2 and photoreceptor cell death: Requirement of motor subunits
Jimeno, D., Lillo, C., Roberts, E. A., Goldstein, L. S. B., & Williams, D. S. (2005) · Experimental Eye Research · doi:10.1016/j.exer.2005.10.026 · Cited by 26 · see citing works
Coupling of ATPase activity, microtubule binding, and mechanics in the dynein motor domain
Niekamp, S., Coudray, N., Zhang, N., Vale, R. D., & Bhabha, G. (2019) · The EMBO Journal · doi:10.15252/embj.2018101414 · Cited by 26 · see citing works
Keeling, E., Chatelet, D. S., Tan, N., Khan, F., Richards, R., Thisainathan, T., Goggin, P., Page, A. M., Tumbarello, D. A., Lotery, A. J., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21218408 · Cited by 26 · see citing works
Actin dynamics in protein homeostasis
Williams, T. D., & Rousseau, A. (2022) · Bioscience Reports · doi:10.1042/bsr20210848 · Cited by 25 · see citing works
Logistics of neuronal protein turnover: Numbers and mechanisms
Sun, C., & Schuman, E. M. (2022) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2022.103793 · Cited by 24 · see citing works
Luthert, P. J., & Kiel, C. (2020) · Network and Systems Medicine · doi:10.1089/nsm.2020.0005 · Cited by 12 · see citing works
Self-citationAerobic Glycolysis in Photoreceptors Supports Energy Demand in the Absence of Mitochondrial Coupling
Hass, D. T., Bisbach, C. M., Sadı́lek, M., Sweet, I. R., & Hurley, J. B. (2023) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-27681-1_64 · Cited by 10 · see citing works
Calculation of ion currents across the inner membrane of functionally intact mitochondria
Kane, D. A., & Pavlov, E. V. (2013) · Channels · doi:10.4161/chan.26290 · Cited by 10 · see citing works
The retinal pigment epithelium displays electrical excitability and lateral signal spreading
Ignatova, I. I., Frolov, R. V., & Nymark, S. (2023) · BMC Biology · doi:10.1186/s12915-023-01559-5 · Cited by 8 · see citing works
Hughes, G. W., Sridhar, P., Nestorow, S. A., Wotherspoon, P. J., Cooper, B. F., & Knowles, T. J. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.06.06.138008 · Cited by 7 · see citing works
Sevrin, T., Strasser, L., Ternet, C., Junk, P., Caffarini, M., Prins, S., D'Arcy, C., Catozzi, S., Oliviero, G., Wynne, K. J., et al. (2022) · iScience · doi:10.1016/j.isci.2023.105931 · Cited by 3 · see citing works
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“Energetics of the outer retina I: Estimates of nutrient exchange and ATP generation”
Prins, S., Kiel, C., Foss, A. J. E., Zouache, M. A., & Luthert, P. J. (2024) · PLoS ONE · doi:10.1371/journal.pone.0312260 · Cited by 2 · see citing works
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- Authors
- Kiel, C., Prins, S., Foss, A. J. E., & Luthert, P. J.
- Affiliations
- University of Pavia (IT)
- University College London (GB)
- Nottingham University Hospitals NHS Trust (GB)
- NIHR Moorfields Biomedical Research Centre (GB)
- Corresponding author
- Kiel, Christina
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2025-01-27
- Volume
- 20
- Issue
- 1
- Pages
- e0311169
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC11771881
- OpenAlex
- W4406875952
- Cited by
- 6
- References
- 70
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 1
- FWCI
- 1.49
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Moorfields Eye Charity (Grant GR001345)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Keywords
- outer retina, retinal energy metabolism, retinal pigment epithelium, photoreceptors, energy balance, circadian rhythm, diurnal variation, age-related macular degeneration, rod and cone photoreceptors, perifovea, fovea, retinal aging
- MeSH terms
- Adenosine Triphosphate, Circadian Rhythm, Energy Metabolism, Humans, Light, Retinal Pigment Epithelium
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