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Mitochondrial absorption of short wavelength light drives primate blue retinal cones into glycolysis which may increase their pace of aging

  • Jaimie Hoh Kam (a1), Tobias W. Weinrich (a1), Harpreet Sangha (a1), Michael B. Powner (a2), Robert Fosbury (a1) (a3) and Glen Jeffery (a1)...


Photoreceptors have high energy demands and densely packed mitochondria through which light passes before phototransduction. Old world primates including humans have three cone photoreceptor types mediating color vision with short (S blue), medium (M green), and long (L red) wavelength sensitivities. However, S-cones are enigmatic. They comprise <10% of the total cone population, their responses saturate early, and they are susceptible in aging and disease. Here, we show that primate S-cones actually have few mitochondria and are fueled by glycolysis, not by mitochondrial respiration. Glycolysis has a limited ability to sustain activity, potentially explaining early S-cone saturation. Mitochondria act as optical filters showing reduced light transmission at 400–450 nm where S-cones are most sensitive (420 nm). This absorbance is likely to arise in a mitochondrial porphyrin that absorbs strongly in the Soret band. Hence, reducing mitochondria will improve S-cone sensitivity but result in increased glycolysis as an alternative energy source, potentially increasing diabetic vulnerability due to restricted glucose access. Further, glycolysis carries a price resulting in premature functional decline as seen in aged S-cones. Soret band absorption may also impact on mitochondrial rich M and L cones by reducing sensitivity at the lower end of their spectral sensitivity range resulting in increased differentiation from S-cone responses. These data add to the list of unique characteristic of S-cones and may also explain aspects of their vulnerability.


Corresponding author

*Address correspondence to: Glen Jeffery, Email:


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Bowmaker, J.K. (2008). Evolution of vertebrate visual pigments. Vision Research 48, 20222041.
Bowmaker, J.K., Astell, S., Hunt, D.M. & Mollon, J.D. (1991). Photosensitive and photostable pigments in the retinae of Old World monkeys. Journal of Experimental Biology 156, 119.
Bowmaker, J.K. & Dartnall, H.J.A. (1980). Visual pigments of rods and cones in the human retina. Journal of Physiology 298, 501511.
Brunet, C., Antoine, R., Lemoine, J. & Dugourd, P. (2012). Soret band of the gas-phase ferri-cytochrome c. Journal of Physical Chemistry Letters 3, 698702.
Cornish, E.E., Xiao, M., Yang, Z., Provis, J.M. & Hendrickson, A.E. (2004). The role of opsin expression and apoptosis in determination of cone types in human retina. Experimental Eye Research 78, 11431154.
Curcio, C.A., Allen, K.A., Sloan, K.R., Lerea, C.L., Hurley, J.B., Klock, I.B. & Milam, A.H. (1991). Distribution and morphology of human cone photoreceptors stained with anti-blue opsin. Journal of Comparative Neurology 312, 610624.
Dartnall, H.J., Bowmaker, J.K. & Mollon, J.D. (1983). Human visual pigments: Microspectrophotometric results from the eyes of seven persons. Proceedings of the Royal Society of London, Series B: Biological Sciences 220, 115130.
Dubey, A.K., Godbole, A. & Mathew, M.K. (2016). Regulation of VDAC trafficking modulates cell death. Cell Death & Disease 2, 16085.
Glenn, J.V. & Stitt, A.W. (2009). The role of advanced glycation end products in retinal ageing and disease. Biochimica et Biophysica Acta 1790, 11091116.
Greenstein, V.C., Hood, D.C., Ritch, R., Steinberger, D. & Carr, R.E. (1989). S (blue) cone pathway vulnerability in retinitis pigmentosa, diabetes and glaucoma. Investigative Ophthalmology & Visual Science 30, 17321737.
Haider, N.B., Jacobson, S.G., Cideciyan, A.V., Swiderski, R., Streb, L.M., Searby, C., Beck, G., Hockey, R., Hanna, D.B., Gorman, S., Duhl, D., Carmi, R., Bennett, J., Weleber, R.G., Fishman, G.A., Wright, A.F., Stone, E.M. & Sheffield, V.C. (2000). Mutation of a nuclear receptor gene, NR2E3, causes enhanced S cone syndrome, a disorder of retinal cell fate. Nature Genetics 24, 127131.
Hoang, Q.V., Linsenmeier, R.A., Chung, C.K. & Curcio, C.A. (2002). Photoreceptor inner segments in monkey and human retina: Mitochondrial density, optics, and regional variation. Visual Neuroscience 19, 395407.
Hurley, J.B., Lindsay, K.J. & Du, J. (2015). Glucose, lactate, and shuttling of metabolites in vertebrate retinas. Journal of Neuroscience Research 93, 10791092.
Kim, J.W., Yang, H.J., Oel, A.P., Brooks, M.J., Jia, L., Plachetzki, D.C., Li, W., Allison, W.T. & Swaroop, A. (2016). Recruitment of rod photoreceptors from short-wavelength-sensitive cones during the evolution of nocturnal vision in mammals. Developmental Cell 37, 520532.
Knowles, A., Davson, H. & Dartnall, H.J.A. (1977). The Photobiology of Vision. Cambridge, MA: Academic Press.
Kram, Y.A., Mantey, S. & Corbo, J.C. (2010). Avian cone photoreceptors tile the retina as five independent, self-organizing mosaics. PLoS One 5, e8992.
Linsenmeier, R.A. (1986). Effects of light and darkness on oxygen distribution and consumption in the cat retina. The Journal of General Physiology 88, 521542.
Linsenmeier, R.A. & Padnick-Silver, L. (2000). Metabolic dependence of photoreceptors on the choroid in the normal and detached retina. Investigative Ophthalmology & Visual Science 41, 31173123.
Milam, A.H., Rose, L., Cideciyan, A.V., Barakett, M.R., Tan, W., Gupta, N., Aleman, T.S., Wright, A.F., Stone, E.M., Sheffied, V.C. & Jacobson, S.G. (2002). The nuclear receptor NB2E3 plays a role in human retinal photoreceptor differentiation and degeneration. Proceedings of the National Academy of Sciences of the United States of America 99, 473478.
Mollon, J.D. (1982). Color vision. Annual Review of Psychology 33, 4185.
Mollon, J.D. & Polden, P.G. (1977). Saturation of a retinal cone mechanism. Nature 265, 243246.
Morshedian, A. & Fain, G.L. (2015). Single-photon sensitivity of lamprey rods with cone-like outer segments. Current Biology 25, 484487.
Nakajima, A., Ishihara, M., Arai, T., Morimoto, Y., Kikuchi, M., Kannari, F. & Obara, M. (1993). Measurement for optical properties of mitochondria in vitro. Proceedings of the Society of Photo-Optical Instrumentation Engineers 1883, 6267.
Narayan, D.S., Chidlow, G., Wood, J.P. & Casson, R.J. (2017). Glucose metabolism in mammalian photoreceptor inner and outer segments. Clinical and Experimental Ophthalmology 45, 730741.
Nihira, M., Anderson, K., Gorin, F.A. & Burns, S.M. (1995). Primate rod and cone photoreceptors may differ in glucose accessibility. Investigative Ophthalmology & Visual Science 36, 12591270.
Nork, T.M., McCormick, S.A., Chao, G.M. & Odom, J.V. (1990). Distribution of carbonic anhydrase among human photoreceptors. Investigative Ophthalmology & Visual Science 31, 14511458.
Ripamonti, C., Aboshiha, J., Henning, G.B., Sergouniotis, P.I., Michaelides, M., Moore, A.T., Webster, A.R. & Stockman, A. (2014). Vision in observers with enhanced s-cone syndrome: An excess of s-cones but connected mainly to conventional s-cone pathways. Investigative Ophthalmology & Visual Science 55, 963976.
Stavenga, D.G. & Wilts, B.D. (2014). Oil droplets of bird eyes: Microlenses acting as spectral filters. Philosophical Transactions of the Royal Society, B: Biological Sciences 369, 20130041.
Stockman, A. & Sharpe, L.T. (1998). Human cone spectral sensitivities: A progress report. Vision Research 38, 31933206.
Sun, L., Huang, T., Xu, W., Sun, J., Lv, Y. & Wang, Y. (2017). Advanced glycation end products promote VEGF expression and thus choroidal neovascularization via Cyr61-PI3K/AKT signaling pathway. Scientific Reports 7, 14925.
Uribarri, J., Woodruff, S., Goodman, S., Cai, W., Chen, X., Pyzik, R., Yong, A., Striker, G.E. & Vlassara, H. (2010). Advanced glycation end products in foods and a practical guide to their reduction in the diet. Journal of the American Dietetic Association 110, 911916.e912.
Vorobyev, M. (2003). Coloured oil droplets enhance colour discrimination. Proceedings of the Royal Society B: Biological Sciences 270, 12551261.
Walls, G.L. (1942). The Vertebrate Eye and its Adaptive Radiation. New York: Hafner Publishing Company.
Weinrich, T.W., Powner, M.B., Lynch, A., Jonnal, R.S., Werner, J.S. & Jeffery, G. (2017). No evidence for loss of short-wavelength sensitive cone photoreceptors in normal ageing of the primate retina. Scientific Reports 7, 46346.
Werner, J.S. (2016). The Verriest Lecture: Short-wave-sensitive cone pathways across the life span. Journal of the Optical Society of America A 33, A104A122.
Wilby, D. & Roberts, N.W. (2017). Optical influence of oil droplets on cone photoreceptor sensitivity. Journal of Experimental Biology 220, 19972004.
Xing, Y., Zhang, X., Song, X., Lv, Z., Hou, L. & Li, F. (2013). Injury of cortical neurons is caused by the advanced glycation end products-mediated pathway. Neural Regeneration Research 8, 909915.


Mitochondrial absorption of short wavelength light drives primate blue retinal cones into glycolysis which may increase their pace of aging

  • Jaimie Hoh Kam (a1), Tobias W. Weinrich (a1), Harpreet Sangha (a1), Michael B. Powner (a2), Robert Fosbury (a1) (a3) and Glen Jeffery (a1)...


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