Abstract
We have adapted intrinsic signal optical imaging of neural activity to the noninvasive functional imaging of the retina. Results to date demonstrate the feasibility and potential of this new method of functional assessment of the retina. In response to visual stimuli, we have imaged reflectance changes in the retina that are robust and spatially colocalized to the sites of stimulation. However, the technique is in its infancy and many questions as to the underlying mechanisms remain. In particular, the source and nature of the activity-dependent intrinsic optical signals in the retina need to be characterized and their anatomic origins determined. The studies described here begin to address these issues. The evidence indicates that the imaged signals are driven by the outer retinal layers and have a dominant hemodynamic component.
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Grinvald A, Lieke E, Frostig RD, Gilbert CD, Wiesel TN. Functional architecture of cortex revealed by optical imaging of intrinsic signals. Nature 1986;324:361–364.
Frostig RD, Lieke EE, Ts’o DY, Grinvald A. Cortical functional architecture and local coupling between neuronal activity and the microcirculation revealed by in vivo high-resolution optical imaging of intrinsic signals. Proc Natl Acad Sci U S A 1990;87:6082–6086.
Ts’o DY, Frostig RD, Lieke EE, Grinvald A. Functional organization of primate visual cortex revealed by high resolution optical imaging. Science 1990;249:417–420.
Haglund MM, Ojemann GA, Hochman DW. Optical imaging of epileptiform and functional activity in human cerebral cortex. Nature 1992;358:668–671.
Toga AW, Cannestra AF, Black KL. The temporal/spatial evolution of optical signals in human cortex. Cereb Cortex 1995;5:561–565.
Cannestra AF, Blood AJ, Black KL, Toga AW. The evolution of optical signals in human and rodent cortex. Neuroimage 1996;3:202–208.
Riva CE, Harino S, Shonat RD, Petrig BL. Flicker evoked increase in optic nerve head blood flow in anesthetized cats. Neurosci Lett 1991;128:291–296.
Linsenmeier RA. Effects of light and darkness on oxygen distribution and consumption in the cat retina. J Gen Physiol 1986;88:521–542.
Hogeboom van Buggenum IM, van der Heijde GL, Tangelder GJ, Reichert-Thoen JW. Ocular oxygen measurement. Brit J Ophthalmol 1996;80:567–573.
Schmidt M, Giessl A, Laufs T, Hankeln T, Wolfrum U, Burmester T. How does the eye breathe? Evidence for neuroglobin-mediated oxygen supply in the mammalian retina. J Biol Chem 2003;278:1932–1935.
Hood DC, Frishman LJ, Viswanathan S, Robson JG, Ahmed J. Evidence for a ganglion cell contribution to the primate electroretinogram (ERG): effects of TTX on the multifocal ERG in macaque. Vis Neurosci 1999;16:411–416.
Hare WA, Ton H. Effects of APB, PDA, and TTX on ERG responses recorded using both multifocal and conventional methods in monkey. Doc Ophthalmol 2002;105:189–222.
Slaughter MM, Miller RF. 2-Amino-4-phosphonobutyric acid: a new pharmacological tool for retina research. Science 1981;211:182–185.
Slaughter M, Miller R. An excitatory amino acid antagonist blocks cone input to sign-conserving second-order retinal neurons. Science 1983;219:1230–1232.
Shmuel A, Augath M, Oeltermann A, Logothetis NK. Negative functional MRI response correlates with decreases in neuronal activity in monkey visual area V1. Nat Neurosci 2006;9:569–577.
Shmuel A, Yacoub E, Pfeuffer J, Van de Moortele PF, Adriany G, Hu X, Ugurbil K. Sustained negative BOLD, blood flow and oxygen consumption response and its coupling to the positive response in the human brain. Neuron 2002;36:1195–1210.
Abramoff MD, Kwon YH, Ts’o D, et al. Visual stimulus-induced changes in human near-infrared fundus reflectance. Invest Ophthalmol Vis Sci 2006;47:715–721.
Tsunoda K, Oguchi Y, Hanazono G, Tanifuji M. Mapping coneand rod-induced retinal responsiveness in macaque retina by optical imaging. Invest Ophthalmol Vis Sci 2004;45:3820–3826.
Nelson DA, Krupsky S, Pollack A, et al. Noninvasive multiparameter functional optical imaging of the eye. Ophthalmic Surg Lasers Imaging 2005;36:57–66.
Hanazono G, Tsunoda K, Shinoda K, Tsubota K, Miyake Y, Tanifuji M. Intrinsic signal imaging in macaque retina reveals different types of flash-induced light reflectance changes of different origins. Invest Ophthalmol Vis Sci 2007;48:2903–2912.
Okawa Y, Fujikado T, Miyoshi T, Hirohara Y, Mihashi T, Tano Y. Contribution of retinal ganglion cell activity to intrinsic signals. Invest Ophthalmol Vis Sci 2007;48:3845.
Duong TQ, Ngan S-C, Ugurbil K, Kim S-G. Functional magnetic resonance imaging of the retina. Invest Ophthalmol Vis Sci 2002;43:1176–1181.
Birol G, Wang S, Budzynski E, Wangsa-Wirawan ND, Linsenmeier RA. Oxygen distribution and consumption in the macaque retina. Am J Physiol Heart Circ Physiol 2007;293:H1696–H1704.
Yao XC, George JS. Dynamic neuroimaging of retinal light responses using fast intrinsic optical signals. Neuroimage 2006;33:898–906.
Cohen LB. Changes in neuron structure during action potential propagation and synaptic transmission. Physiol Rev 1973;53:373–418.
Schallek JB, Li H, Kardon RH, et al. Stimulus-evoked intrinsic optical signals in the retina: spatial and temporal characteristics. Invest Ophthalmol Vis Sci 2009 (in press).
Schallek JB, Kardon RH, Kwon YH, Abramoff MD, Soliz P, Ts’o D. Stimulus-evoked intrinsic optical signals in the retina: pharmacological dissection reveals outer retinal origins. Invest Ophthalmol Vis Sci 2009 (in press).
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Ts’o, D., Schallek, J., Kwon, Y. et al. Noninvasive functional imaging of the retina reveals outer retinal and hemodynamic intrinsic optical signal origins. Jpn J Ophthalmol 53, 334–344 (2009). https://doi.org/10.1007/s10384-009-0687-2
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DOI: https://doi.org/10.1007/s10384-009-0687-2