1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Vision Science
  4. Volume 5, 2019
  5. Article

Annual Review of Vision Science

Volume 5, 2019

Imaging Retinal Activity in the Living Eye

Abstract

Retinal function has long been studied with psychophysical methods in humans, whereas detailed functional studies of vision have been conducted mostly in animals owing to the invasive nature of physiological approaches. There are exceptions to this generalization, for example, the electroretinogram. This review examines exciting recent advances using in vivo retinal imaging to understand the function of retinal neurons. In some cases, the methods have existed for years and are still being optimized. In others, new methods such as optophysiology are revealing novel patterns of retinal function in animal models that have the potential to change our understanding of the functional capacity of the retina. Together, the advances in retinal imaging mark an important milestone that shifts attention away from anatomy alone and begins to probe the function of healthy and diseased eyes.

Keyword(s): adaptive optics, calcium indicator, functional imaging, intrinsic signals, neurovascular coupling, optical coherence tomography
Loading

Article metrics loading...

/content/journals/10.1146/annurev-vision-091517-034239
2019-09-15
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/vision/5/1/annurev-vision-091517-034239.html?itemId=/content/journals/10.1146/annurev-vision-091517-034239&mimeType=html&fmt=ahah

Literature Cited

  1. Abramoff MD, Kwon YH, Ts'o D, Soliz P, Zimmerman B et al. 2006. Visual stimulus-induced changes in human near-infrared fundus reflectance. Investig. Ophthalmol. Vis. Sci. 47:715–21
     [Google Scholar]
  2. Akerboom J, Carreras Calderon N, Tian L, Wabnig S, Prigge M et al. 2013. Genetically encoded calcium indicators for multi-color neural activity imaging and combination with optogenetics. Front. Mol. Neurosci. 6:2
     [Google Scholar]
  3. Alm A, Bill A. 1970. Blood flow and oxygen extraction in the cat uvea at normal and high intraocular pressures. Acta Physiol. Scand. 80:19–28
     [Google Scholar]
  4. Ames A 3rd, Li YY, Heher EC, Kimble CR 1992. Energy metabolism of rabbit retina as related to function: high cost of Na+ transport. J. Neurosci. 12:840–53
     [Google Scholar]
  5. Asteriti S, Liu CH, Hardie RC 2017. Calcium signalling in Drosophila photoreceptors measured with GCaMP6f. Cell Calcium 65:40–51
     [Google Scholar]
  6. Bar-Noam AS, Farah N, Shoham S 2016. Correction-free remotely scanned two-photon in vivo mouse retinal imaging. Light Sci. Appl. 5:e16007
     [Google Scholar]
  7. Beach JM, Schwenzer KJ, Srinivas S, Kim D, Tiedeman JS 1999. Oximetry of retinal vessels by dual-wavelength imaging: calibration and influence of pigmentation. J. Appl. Physiol. 86:748–58
     [Google Scholar]
  8. Bedggood P, Metha A. 2012. Variability in bleach kinetics and amount of photopigment between individual foveal cones. Investig. Ophthalmol. Vis. Sci. 53:73673–81
     [Google Scholar]
  9. Blair NP, Wanek J, Felder AE, Joslin CE, Kresovich JK et al. 2017. Retinal oximetry and vessel diameter measurements with a commercially available scanning laser ophthalmoscope in diabetic retinopathy. Investig. Ophthalmol. Vis. Sci. 58:5556–63
     [Google Scholar]
  10. Borghuis BG, Marvin JS, Looger LL, Demb JB 2013. Two-photon imaging of nonlinear glutamate release dynamics at bipolar cell synapses in the mouse retina. J. Neurosci. 33:10972–85
     [Google Scholar]
  11. Campbell FW, Rushton WA. 1955. Measurement of the scotopic pigment in the living human eye. J. Physiol. 130:131–47
     [Google Scholar]
  12. Chance B, Schoener B, Oshino R, Itshak F, Nakase Y 1979. Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples. NADH and flavoprotein fluorescence signals. J. Biol. Chem. 254:4764–71
     [Google Scholar]
  13. Chen C, Tsina E, Cornwall MC, Crouch RK, Vijayaraghavan S, Koutalos Y 2005. Reduction of all-trans retinal to all-trans retinol in the outer segments of frog and mouse rod photoreceptors. Biophys. J. 88:2278–87
     [Google Scholar]
  14. Cheong SK, Strazzeri JM, Williams DR, Merigan WH 2018. All-optical recording and stimulation of retinal neurons in vivo in retinal degeneration mice. PLOS ONE 13:e0194947
     [Google Scholar]
  15. Choi KE, Yun C, Kim YH, Kim SW, Oh J, Huh K 2017. The effect of photopigment bleaching on fundus autofluorescence in acute central serous chorioretinopathy. Retina 37:568–77
     [Google Scholar]
  16. Cohen LB. 1973. Changes in neuron structure during action potential propagation and synaptic transmission. Physiol. Rev. 53:373–418
     [Google Scholar]
  17. Cohen LB, Salzberg BM. 1978. Optical measurement of membrane potential. Rev. Physiol. Biochem. Pharmacol. 83:35–88
     [Google Scholar]
  18. Cooper RF, Tuten WS, Dubra A, Brainard DH, Morgan JIW 2017. Non-invasive assessment of human cone photoreceptor function. Biomed. Opt. Express 8:5098–112
     [Google Scholar]
  19. DeLint PJ, Berendschot TT, van de Kraats J, van Norren D 2000. Slow optical changes in human photoreceptors induced by light. Investig. Ophthalmol. Vis. Sci. 41:282–89
     [Google Scholar]
  20. Duebel J, Haverkamp S, Schleich W, Feng G, Augustine GJ et al. 2006. Two-photon imaging reveals somatodendritic chloride gradient in retinal ON-type bipolar cells expressing the biosensor Clomeleon. Neuron 49:81–94
     [Google Scholar]
  21. Duong TQ. 2014. Magnetic resonance imaging of the retina: from mice to men. Magn. Reson. Med. 71:1526–30
     [Google Scholar]
  22. Duong TQ, Kim DS, Ugurbil K, Kim SG 2002. Functional magnetic resonance imaging of the retina. Investig. Ophthalmol. Vis. Sci. 43:41176
     [Google Scholar]
  23. Elner SG, Elner VM, Field MG, Park S, Heckenlively JR, Petty HR 2008. Retinal flavoprotein autofluorescence as a measure of retinal health. Trans. Am. Ophthalmol. Soc. 106:215–22
     [Google Scholar]
  24. Elsner AE, Burns SA, Hughes GW, Webb RH 1992. Reflectometry with a scanning laser ophthalmoscope. Appl. Opt. 31:3697–710
     [Google Scholar]
  25. Erchova I, Tumlinson AR, Fergusson J, White N, Drexler W et al. 2018. Optophysiological characterisation of inner retina responses with high-resolution optical coherence tomography. Sci. Rep. 8:1813
     [Google Scholar]
  26. Fan N, Silverman SM, Liu Y, Wang X, Kim BJ et al. 2017. Rapid repeatable in vivo detection of retinal reactive oxygen species. Exp. Eye Res. 161:71–81
     [Google Scholar]
  27. Feke GT, Riva CE. 1978. Laser Doppler measurements of blood velocity in human retinal vessels. J. Opt. Soc. Am. 68:526–31
     [Google Scholar]
  28. Feke GT, Zuckerman R, Green GJ, Weiter JJ 1983. Response of human retinal blood flow to light and dark. Investig. Ophthalmol. Vis. Sci. 24:136–41
     [Google Scholar]
  29. Field MG, Comer GM, Kawaji T, Petty HR, Elner VM 2012. Noninvasive imaging of mitochondrial dysfunction in dry age-related macular degeneration. Ophthalmic Surg. Lasers Imaging 43:358–65
     [Google Scholar]
  30. Fox MD, Raichle ME. 2007. Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat. Rev. Neurosci. 8:700–11
     [Google Scholar]
  31. Frostig RD, Lieke EE, Ts'o DY, Grinvald A 1990. Cortical functional architecture and local coupling between neuronal activity and the microcirculation revealed by in vivo high-resolution optical imaging of intrinsic signals. PNAS 87:6082–6
     [Google Scholar]
  32. Garhöfer G, Bek T, Boehm AG, Gherghel D, Grunwald J et al. 2010. Use of the retinal vessel analyzer in ocular blood flow research. Acta Ophthalmol 88:717–22
     [Google Scholar]
  33. Garhöfer G, Zawinka C, Resch H, Kothy P, Schmetterer L, Dorner GT 2004. Reduced response of retinal vessel diameters to flicker stimulation in patients with diabetes. Br. J. Ophthalmol. 88:887–91
     [Google Scholar]
  34. Geirsdottir A, Palsson O, Hardarson SH, Olafsdottir OB, Kristjansdottir JV, Stefánsson E 2012. Retinal vessel oxygen saturation in healthy individuals. Investig. Ophthalmol. Vis. Sci. 53:5433–42
     [Google Scholar]
  35. Grieve K, Roorda A. 2008. Intrinsic signals from human cone photoreceptors. Investig. Ophthalmol. Vis. Sci. 49:713–19
     [Google Scholar]
  36. Grinvald A, Lieke E, Frostig RD, Gilbert CD, Wiesel TN 1986. Functional architecture of cortex revealed by optical imaging of intrinsic signals. Nature 324:361–64
     [Google Scholar]
  37. Guevara-Torres A, Joseph A, Schallek JB 2016. Label free measurement of retinal blood cell flux, velocity, hematocrit and capillary width in the living mouse eye. Biomed. Opt. Express 7:4228–49
     [Google Scholar]
  38. Gulshan V, Peng L, Coram M, Stumpe MC, Wu D et al. 2016. Development and validation of a deep learning algorithm for detection of diabetic retinopathy in retinal fundus photographs. JAMA 316:2402–10
     [Google Scholar]
  39. Hanazono G, Tsunoda K, Kazato Y, Suzuki W, Tanifuji M 2012. Functional topography of rod and cone photoreceptors in macaque retina determined by retinal densitometry. Investig. Ophthalmol. Vis. Sci. 53:2796–803
     [Google Scholar]
  40. Hanazono G, Tsunoda K, Kazato Y, Tsubota K, Tanifuji M 2008. Evaluating neural activity of retinal ganglion cells by flash-evoked intrinsic signal imaging in macaque retina. Investig. Ophthalmol. Vis. Sci. 49:4655–63
     [Google Scholar]
  41. Hanazono G, Tsunoda K, Shinoda K, Tsubota K, Miyake Y, Tanifuji M 2007. Intrinsic signal imaging in macaque retina reveals different types of flash-induced light reflectance changes of different origins. Investig. Ophthalmol. Vis. Sci. 48:2903–12
     [Google Scholar]
  42. Hecht S, Haig C, Chase AM 1937. The influence of light adaptation on subsequent dark adaptation of the eye. J. Gen. Physiol. 20:831–50
     [Google Scholar]
  43. Heikal AA. 2010. Intracellular coenzymes as natural biomarkers for metabolic activities and mitochondrial anomalies. Biomark. Med. 4:241–63
     [Google Scholar]
  44. Hickam JB, Frayser R. 1966. Studies of the retinal circulation in man. Observations on vessel diameter, arteriovenous oxygen difference, and mean circulation time. Circulation 33:302–16
     [Google Scholar]
  45. Hill DK, Keynes RD. 1949. Opacity changes in stimulated nerve. J. Physiol. 108:278–81
     [Google Scholar]
  46. Hillmann D, Spahr H, Pfäffle C, Sudkamp H, Franke G, Huttmann G 2016. In vivo optical imaging of physiological responses to photostimulation in human photoreceptors. PNAS 113:13138–43
     [Google Scholar]
  47. Hochbaum DR, Zhao Y, Farhi SL, Klapoetke N, Werley CA et al. 2014. All-optical electrophysiology in mammalian neurons using engineered microbial rhodopsins. Nat. Methods 11:825–33
     [Google Scholar]
  48. Hofer H, Carroll J, Neitz J, Neitz M, Williams DR 2005. Organization of the human trichromatic cone mosaic. J. Neurosci. 25:9669–79
     [Google Scholar]
  49. Hofmann KP, Uhl R, Hoffmann W, Kreutz W 1976. Measurements on fast light-induced light-scattering and -absorption changes in outer segments of vertebrate light sensitive rod cells. Biophys. Struct. Mech. 2:61–77
     [Google Scholar]
  50. Huang S, Heikal AA, Webb WW 2002. Two-photon fluorescence spectroscopy and microscopy of NAD(P)H and flavoprotein. Biophys. J. 82:2811–25
     [Google Scholar]
  51. Imanishi Y, Batten ML, Piston DW, Baehr W, Palczewski K 2004. Noninvasive two-photon imaging reveals retinyl ester storage structures in the eye. J. Cell Biol. 164:373–83
     [Google Scholar]
  52. Izhaky D, Nelson DA, Burgansky-Eliash Z, Grinvald A 2009. Functional imaging using the retinal function imager: direct imaging of blood velocity, achieving fluorescein angiography-like images without any contrast agent, qualitative oximetry, and functional metabolic signals. Jpn. J. Ophthalmol. 53:345–51
     [Google Scholar]
  53. Jia Y, Bailey ST, Hwang TS, McClintic SM, Gao SS et al. 2015. Quantitative optical coherence tomography angiography of vascular abnormalities in the living human eye. PNAS 112:E2395–402
     [Google Scholar]
  54. Keynes RD. 1951. The ionic movements during nervous activity. J. Physiol. 114:119–50
     [Google Scholar]
  55. Kiser PD, Golczak M, Maeda A, Palczewski K 2012. Key enzymes of the retinoid (visual) cycle in vertebrate retina. Biochim. Biophys. Acta 1821:137–51
     [Google Scholar]
  56. Klapoetke NC, Murata Y, Kim SS, Pulver SR, Birdsey-Benson A et al. 2014. Independent optical excitation of distinct neural populations. Nat. Methods 11:338–46
     [Google Scholar]
  57. Kocaoglu OP, Liu Z, Zhang F, Kurokawa K, Jonnal RS, Miller DT 2016. Photoreceptor disc shedding in the living human eye. Biomed. Opt. Express 7:4554–68
     [Google Scholar]
  58. Kornfield TE, Newman EA. 2014. Regulation of blood flow in the retinal trilaminar vascular network. J. Neurosci. 34:11504–13
     [Google Scholar]
  59. Lamb TD, Pugh EN Jr. 2004. Dark adaptation and the retinoid cycle of vision. Prog. Retin. Eye Res. 23:307–80
     [Google Scholar]
  60. Leitgeb RA, Werkmeister RM, Blatter C, Schmetterer L 2014. Doppler optical coherence tomography. Prog. Retin. Eye Res. 41:26–43
     [Google Scholar]
  61. Lennie P. 2003. The cost of cortical computation. Curr. Biol. 13:493–97
     [Google Scholar]
  62. Liem AT, Keunen JE, Van Norren D 1996. Clinical applications of fundus reflection densitometry. Surv. Ophthalmol. 41:37–50
     [Google Scholar]
  63. Liem AT, Keunen JE, van Norren D, van de Kraats J 1991. Rod densitometry in the aging human eye. Investig. Ophthalmol. Vis. Sci. 32:2676–82
     [Google Scholar]
  64. Ling T, Boyle KC, Goetz G, Zhou P, Quan Y et al. 2018. Full-field interferometric imaging of propagating action potentials. Light Sci. Appl. 7:107
     [Google Scholar]
  65. Lu CD, Lee B, Schottenhamml J, Maier A, Pugh EN Jr., Fujimoto JG 2017. Photoreceptor layer thickness changes during dark adaptation observed with ultrahigh-resolution optical coherence tomography. Investig. Ophthalmol. Vis. Sci. 58:4632–43
     [Google Scholar]
  66. Maclaurin D, Venkatachalam V, Lee H, Cohen AE 2013. Mechanism of voltage-sensitive fluorescence in a microbial rhodopsin. PNAS 110:5939–44
     [Google Scholar]
  67. Malonek D, Dirnagl U, Lindauer U, Yamada K, Kanno I, Grinvald A 1997. Vascular imprints of neuronal activity: relationships between the dynamics of cortical blood flow, oxygenation, and volume. c: hanges following sensory stimulation. PNAS 94:14826–31
     [Google Scholar]
  68. Malonek D, Grinvald A. 1996. Interactions between electrical activity and cortical microcirculation revealed by imaging spectroscopy: implications for functional brain mapping. Science 272:551–54
     [Google Scholar]
  69. Martin JA, Roorda A. 2005. Direct and noninvasive assessment of parafoveal capillary leukocyte velocity. Ophthalmology 112:2219–24
     [Google Scholar]
  70. Martin JA, Roorda A. 2009. Pulsatility of parafoveal capillary leukocytes. Exp. Eye Res. 88:356–60
     [Google Scholar]
  71. Masella BD, Hunter JJ, Williams DR 2014. New wrinkles in retinal densitometry. Investig. Ophthalmol. Vis. Sci. 55:7525–34
     [Google Scholar]
  72. McGregor JE, Yin L, Yang Q, Godat T, Huynh KT et al. 2018. Functional architecture of the foveola revealed in the living primate. PLOS ONE 13:e0207102
     [Google Scholar]
  73. Michaelson IC, Friedenwald JS. 1954. Retinal Circulation in Man and Animals Springfield, IL: Charles C Thomas
  74. Mihashi T, Okawa Y, Miyoshi T, Kitaguchi Y, Hirohara Y, Fujikado T 2011. Comparing retinal reflectance changes elicited by transcorneal electrical retinal stimulation with those of optic chiasma stimulation in cats. Jpn. J. Ophthalmol. 55:49–56
     [Google Scholar]
  75. Miura Y. 2018. Two-photon microscopy (TPM) and fluorescence lifetime imaging microscopy (FLIM) of retinal pigment epithelium (RPE) of mice in vivo. Methods Mol. Biol. 1753:73–88
     [Google Scholar]
  76. Morgan JI, Pugh EN Jr. 2013. Scanning laser ophthalmoscope measurement of local fundus reflectance and autofluorescence changes arising from rhodopsin bleaching and regeneration. Investig. Ophthalmol. Vis. Sci. 54:2048–59
     [Google Scholar]
  77. Naderian A, Bussieres L, Thomas S, Lesage F, Casanova C 2017. Cellular origin of intrinsic optical signals in the rabbit retina. Vis. Res. 137:40–49
     [Google Scholar]
  78. Nelson DA, Krupsky S, Pollack A, Aloni E, Belkin M et al. 2005. Special report: noninvasive multi-parameter functional optical imaging of the eye. Ophthalmic Surg. Lasers Imaging 36:57–66
     [Google Scholar]
  79. Newman EA. 2013. Functional hyperemia and mechanisms of neurovascular coupling in the retinal vasculature. J. Cereb. Blood Flow Metab. 33:1685–95
     [Google Scholar]
  80. Nguyen JP, Linder AN, Plummer GS, Shaevitz JW, Leifer AM 2017. Automatically tracking neurons in a moving and deforming brain. PLOS Comput. Biol. 13:e1005517
     [Google Scholar]
  81. Nikonov SS, Kholodenko R, Lem J, Pugh EN Jr. 2006. Physiological features of the S- and M-cone photoreceptors of wild-type mice from single-cell recordings. J. Gen. Physiol. 127:359–74
     [Google Scholar]
  82. O'Connell RA, Anderson AJ, Hosking SL, Batcha AH, Bui BV 2014. Test-retest reliability of retinal oxygen saturation measurement. Optom. Vis. Sci. 91:608–14
     [Google Scholar]
  83. Ogawa S, Lee TM, Kay AR, Tank DW 1990. Brain magnetic resonance imaging with contrast dependent on blood oxygenation. PNAS 87:9868–72
     [Google Scholar]
  84. Okawa Y, Fujikado T, Miyoshi T, Sawai H, Kusaka S et al. 2007. Optical imaging to evaluate retinal activation by electrical currents using suprachoroidal-transretinal stimulation. Investig. Ophthalmol. Vis. Sci. 48:4777–84
     [Google Scholar]
  85. Park SJ, Kim IJ, Looger LL, Demb JB, Borghuis BG 2014. Excitatory synaptic inputs to mouse on-off direction-selective retinal ganglion cells lack direction tuning. J. Neurosci. 34:3976–81
     [Google Scholar]
  86. Peng Q, Zhang Y, Nateras OS, van Osch MJ, Duong TQ 2011. MRI of blood flow of the human retina. Magn. Reson. Med. 65:1768–75
     [Google Scholar]
  87. Pfäffle C, Hillmann D, Spahr H, Kutzner L, Burhan S et al. 2018. Functional imaging of ganglion and receptor cells in living human retina by osmotic contrast. arXiv:1809.02812 [physics.bio-ph.]
  88. Prieto PM, McLellan JS, Burns SA 2005. Investigating the light absorption in a single pass through the photoreceptor layer by means of the lipofuscin fluorescence. Vis. Res. 45:1957–65
     [Google Scholar]
  89. Prunty MC, Aung MH, Hanif AM, Allen RS, Chrenek MA et al. 2015. In vivo imaging of retinal oxidative stress using a reactive oxygen species-activated fluorescent probe. Investig. Ophthalmol. Vis. Sci. 56:5862–70
     [Google Scholar]
  90. Rayner CL, Gole GA, Bottle SE, Barnett NL 2014. Dynamic, in vivo, real-time detection of retinal oxidative status in a model of elevated intraocular pressure using a novel, reversibly responsive, profluorescent nitroxide probe. Exp. Eye Res. 129:48–56
     [Google Scholar]
  91. Riva CE, Harino S, Shonat RD, Petrig BL 1991. Flicker evoked increase in optic nerve head blood flow in anesthetized cats. Neurosci. Lett. 128:291–96
     [Google Scholar]
  92. Riva CE, Ross B, Benedek G 1972. Laser Doppler measurements of blood flow in capillary tubes and retinal arteries. Investig. Ophthalmol. Vis. Sci. 11:936–44
     [Google Scholar]
  93. Roorda A, Williams DR. 1999. The arrangement of the three cone classes in the living human eye. Nature 397:520–22
     [Google Scholar]
  94. Roy CS, Sherrington CS. 1890. On the regulation of the blood-supply of the brain. J. Physiol. 11:85–158.17
     [Google Scholar]
  95. Rushton WA. 1956. The difference spectrum and the photosensitivity of rhodopsin in the living human eye. J. Physiol. 134:11–29
     [Google Scholar]
  96. Sabesan R, Hofer H, Roorda A 2015. Characterizing the human cone photoreceptor mosaic via dynamic photopigment densitometry. PLOS ONE 10:e0144891
     [Google Scholar]
  97. Sabesan R, Schmidt BP, Tuten WS, Roorda A 2016. The elementary representation of spatial and color vision in the human retina. Sci. Adv. 2:e1600797
     [Google Scholar]
  98. Schallek JB, Geng Y, Nguyen H, Williams DR 2013. Morphology and topography of retinal pericytes in the living mouse retina using in vivo adaptive optics imaging and ex vivo characterization. Investig. Ophthalmol. Vis. Sci. 54:8237–50
     [Google Scholar]
  99. Schallek JB, Kardon R, Kwon Y, Abramoff M, Soliz P, Ts'o D 2009a. Stimulus-evoked intrinsic optical signals in the retina: Pharmacologic dissection reveals outer retinal origins. Investig. Ophthalmol. Vis. Sci. 50:4873–80
     [Google Scholar]
  100. Schallek JB, Li H, Kardon R, Kwon Y, Abramoff M et al. 2009b. Stimulus-evoked intrinsic optical signals in the retina: spatial and temporal characteristics. Investig. Ophthalmol. Vis. Sci. 50:4865–72
     [Google Scholar]
  101. Schallek JB, McLellan GJ, Viswanathan S, Ts'o DY 2012. Retinal intrinsic optical signals in a cat model of primary congenital glaucoma. Investig. Ophthalmol. Vis. Sci. 53:1971–81
     [Google Scholar]
  102. Schallek JB, Ts'o D. 2011. Blood contrast agents enhance intrinsic signals in the retina: evidence for an underlying blood volume. c: omponent. Investig. Ophthalmol. Vis. Sci. 52:1325–35
     [Google Scholar]
  103. Schwarz C, Sharma R, Cheong SK, Keller M, Williams DR, Hunter JJ 2018. Selective S cone damage and retinal remodeling following intense ultrashort pulse laser exposures in the near-infrared. Investig. Ophthalmol. Vis. Sci. 59:5973–84
     [Google Scholar]
  104. Schwarz C, Sharma R, Fischer WS, Chung M, Palczewska G et al. 2016. Safety assessment in macaques of light exposures for functional two-photon ophthalmoscopy in humans. Biomed. Opt. Express 7:5148–69
     [Google Scholar]
  105. Schweitzer D, Hammer M, Kraft J, Thamm E, Konigsdorffer E, Strobel J 1999. In vivo measurement of the oxygen saturation of retinal vessels in healthy volunteers. IEEE Trans. Biomed. Eng. 46:1454–65
     [Google Scholar]
  106. Sharma R, Schwarz C, Hunter JJ, Palczewska G, Palczewski K, Williams DR 2017. Formation and clearance of all-trans-retinol in rods investigated in the living primate eye with two-photon ophthalmoscopy. Investig. Ophthalmol. Vis. Sci. 58:604–13
     [Google Scholar]
  107. Sharma R, Schwarz C, Williams DR, Palczewska G, Palczewski K, Hunter JJ 2016a. In vivo two-photon fluorescence kinetics of primate rods and cones. Investig. Ophthalmol. Vis. Sci. 57:647–57
     [Google Scholar]
  108. Sharma R, Williams DR, Palczewska G, Palczewski K, Hunter JJ 2016b. Two-photon autofluorescence imaging reveals cellular structures throughout the retina of the living primate eye. Investig. Ophthalmol. Vis. Sci. 57:632–46
     [Google Scholar]
  109. Shmuel A, Yacoub E, Pfeuffer J, Van de Moortele PF, Adriany G et al. 2002. Sustained negative BOLD, blood flow and oxygen consumption response and its coupling to the positive response in the human brain. Neuron 36:1195–210
     [Google Scholar]
  110. Singh AS, Kolbitsch C, Schmoll T, Leitgeb RA 2010. Stable absolute flow estimation with Doppler OCT based on virtual circumpapillary scans. Biomed. Opt. Express 1:1047–58
     [Google Scholar]
  111. Stefánsson E, Olafsdottir OB, Einarsdottir AB, Eliasdottir TS, Eysteinsson T et al. 2017. Retinal oximetry discovers novel biomarkers in retinal and brain diseases. Investig. Ophthalmol. Vis. Sci. 58:BIO27–33
     [Google Scholar]
  112. Stepanenko OV, Verkhusha VV, Kuznetsova IM, Uversky VN, Turoverov KK 2008. Fluorescent proteins as biomarkers and biosensors: throwing color lights on molecular and cellular processes. Curr. Protein Pept. Sci. 9:338–69
     [Google Scholar]
  113. Stockman A, Sharpe LT. 2000. The spectral sensitivities of the middle- and long-wavelength-sensitive cones derived from measurements in observers of known genotype. Vis. Res. 40:1711–37
     [Google Scholar]
  114. Stokes GG. 1863. On the reduction and oxidation of the colouring matter of the blood. Proc. R. Soc. Lond. 13:355–64
     [Google Scholar]
  115. Suzuki W, Tsunoda K, Hanazono G, Tanifuji M 2013. Stimulus-induced changes of reflectivity detected by optical coherence tomography in macaque retina. Investig. Ophthalmol. Vis. Sci. 54:6345–54
     [Google Scholar]
  116. Tam J, Roorda A. 2011. Speed quantification and tracking of moving objects in adaptive optics scanning laser ophthalmoscopy. J. Biomed. Opt. 16:036002
     [Google Scholar]
  117. Thapa D, Wang B, Lu Y, Son T, Yao X 2017. Enhancement of intrinsic optical signal recording with split spectrum optical coherence tomography. J. Mod. Opt. 64:1800–7
     [Google Scholar]
  118. Theelen T, Berendschot TT, Boon CJ, Hoyng CB, Klevering BJ 2008. Analysis of visual pigment by fundus autofluorescence. Exp. Eye Res. 86:296–304
     [Google Scholar]
  119. Thestrup T, Litzlbauer J, Bartholomaus I, Mues M, Russo L et al. 2014. Optimized ratiometric calcium sensors for functional in vivo imaging of neurons and T lymphocytes. Nat. Methods 11:175–82
     [Google Scholar]
  120. Ts'o DY, Frostig RD, Lieke EE, Grinvald A 1990. Functional organization of primate visual cortex revealed by high resolution optical imaging. Science 249:417–20
     [Google Scholar]
  121. Ts'o DY, Schallek J, Kwon Y, Kardon R, Abramoff M, Soliz P 2009. Noninvasive functional imaging of the retina reveals outer retinal and hemodynamic intrinsic optical signal origins. Jpn. J. Ophthalmol. 53:334–44
     [Google Scholar]
  122. Tsunoda K, Oguchi Y, Hanazono G, Tanifuji M 2004. Mapping cone- and rod-induced retinal responsiveness in macaque retina by optical imaging. Investig. Ophthalmol. Vis. Sci. 45:3820–26
     [Google Scholar]
  123. Uddin MI, Evans SM, Craft JR, Capozzi ME, McCollum GW et al. 2016. In vivo imaging of retinal hypoxia in a model of oxygen-induced retinopathy. Sci. Rep. 6:31011
     [Google Scholar]
  124. Uddin MI, Jayagopal A, McCollum GW, Yang R, Penn JS 2017. In vivo imaging of retinal hypoxia using HYPOX-4-dependent fluorescence in a mouse model of laser-induced retinal vein occlusion (RVO). Investig. Ophthalmol. Vis. Sci. 58:3818–24
     [Google Scholar]
  125. van de Kraats J, Berendschot TT, van Norren D 1996. The pathways of light measured in fundus reflectometry. Vis. Res. 36:2229–47
     [Google Scholar]
  126. van Norren D, van de Kraats J 1989. Imaging retinal densitometry with a confocal scanning laser ophthalmoscope. Vis. Res. 29:1825–30
     [Google Scholar]
  127. Vanzetta I, Deneux T, Grinvald A 2014. High-resolution wide-field optical imaging of microvascular characteristics: from the neocortex to the eye. Neurovascular Coupling Methods M Zhao, H Ma, TH Schwartz 123–59 New York: Humana Press
     [Google Scholar]
  128. Vo Van Toi, Riva CE 1995. Variations of blood flow at optic nerve head induced by sinusoidal flicker stimulation in cats. J. Physiol 482:Pt. 1189–202 Erratum 1995. J. Physiol 484:Pt. 3811
     [Google Scholar]
  129. Wall NR, Wickersham IR, Cetin A, De La Parra M, Callaway EM 2010. Monosynaptic circuit tracing in vivo through Cre-dependent targeting and complementation of modified rabies virus. PNAS 107:21848–53
     [Google Scholar]
  130. Walters S, Schwarz C, Sharma R, Rossi EA, Fischer W et al. 2019. Cellular-scale evaluation of induced photoreceptor degeneration in the living primate eye. Biomed. Opt. Express 10:66–82
     [Google Scholar]
  131. Wang B, Lu Y, Yao X 2016. In vivo optical coherence tomography of stimulus-evoked intrinsic optical signals in mouse retinas. J. Biomed. Opt. 21:96010
     [Google Scholar]
  132. Wang JS, Kefalov VJ. 2011. The cone-specific visual cycle. Prog. Retin. Eye Res. 30:115–28
     [Google Scholar]
  133. Wang TM, Holzhausen LC, Kramer RH 2014. Imaging an optogenetic pH sensor reveals that protons mediate lateral inhibition in the retina. Nat. Neurosci. 17:262–68
     [Google Scholar]
  134. Wells-Gray EM, Choi SS, Zawadzki RJ, Finn SC, Greiner C et al. 2018. Volumetric imaging of rod and cone photoreceptor structure with a combined adaptive optics-optical coherence tomography-scanning laser ophthalmoscope. J. Biomed. Opt. 23:1–15
     [Google Scholar]
  135. Wong-Riley MT. 2010. Energy metabolism of the visual system. Eye Brain 2:99–116
     [Google Scholar]
  136. Xu Y, Zou P, Cohen AE 2017. Voltage imaging with genetically encoded indicators. Curr. Opin. Chem. Biol. 39:1–10
     [Google Scholar]
  137. Yang HH, St-Pierre F, Sun X, Ding X, Lin MZ, Clandinin TR 2016. Subcellular imaging of voltage and calcium signals reveals neural processing in vivo. Cell 166:245–57
     [Google Scholar]
  138. Yao X, Wang B. 2015. Intrinsic optical signal imaging of retinal physiology: a review. J. Biomed. Opt. 20:090901
     [Google Scholar]
  139. Yellen G, Mongeon R. 2015. Quantitative two-photon imaging of fluorescent biosensors. Curr. Opin. Chem. Biol. 27:24–30
     [Google Scholar]
  140. Yin L, Geng Y, Osakada F, Sharma R, Cetin AH et al. 2013. Imaging light responses of retinal ganglion cells in the living mouse eye. J. Neurophysiol. 109:2415–21
     [Google Scholar]
  141. Yin L, Masella B, Dalkara D, Zhang J, Flannery JG et al. 2014. Imaging light responses of foveal ganglion cells in the living macaque eye. J. Neurosci. 34:6596–605
     [Google Scholar]
  142. Yu DY, Cringle SJ. 2001. Oxygen distribution and consumption within the retina in vascularised and avascular retinas and in animal models of retinal disease. Prog. Retin. Eye Res. 20:175–208
     [Google Scholar]
  143. Yuan S, Roney CA, Wierwille J, Chen CW, Xu B et al. 2010. Co-registered optical coherence tomography and fluorescence molecular imaging for simultaneous morphological and molecular imaging. Phys. Med. Biol. 55:191–206
     [Google Scholar]
  144. Zhang LL, Pathak HR, Coulter DA, Freed MA, Vardi N 2006. Shift of intracellular chloride concentration in ganglion and amacrine cells of developing mouse retina. J. Neurophysiol. 95:2404–16
     [Google Scholar]
  145. Zhang P, Zawadzki RJ, Goswami M, Nguyen PT, Yarov-Yarovoy V et al. 2017. In vivo optophysiology reveals that G-protein activation triggers osmotic swelling and increased light scattering of rod photoreceptors. PNAS 114:E2937–46
     [Google Scholar]
  146. Zhang Q, Lu R, Wang B, Messinger JD, Curcio CA, Yao X 2015. Functional optical coherence tomography enables in vivo physiological assessment of retinal rod and cone photoreceptors. Sci. Rep. 5:9595
     [Google Scholar]
  147. Zhang QX, Lu RW, Li YG, Yao XC 2011. In vivo confocal imaging of fast intrinsic optical signals correlated with frog retinal activation. Opt. Lett. 36:4692–94
     [Google Scholar]
  148. Zhong Z, Huang G, Chui TY, Petrig BL, Burns SA 2012. Local flicker stimulation evokes local retinal blood velocity changes. J. Vis. 12:3
     [Google Scholar]
/content/journals/10.1146/annurev-vision-091517-034239
Loading
Imaging Retinal Activity in the Living Eye
Annual Review of Vision Science 5, 15 (2019); https://doi.org/10.1146/annurev-vision-091517-034239
/content/journals/10.1146/annurev-vision-091517-034239
/content/journals/10.1146/annurev-vision-091517-034239
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error