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Photoresponses of human rods in vivo derived from paired-flash electroretinograms

Published online by Cambridge University Press:  02 June 2009

David R. Pepperberg
Affiliation:
Lions of Illinois Eye Research Institute, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago College of Medicine, Chicago
David G. Birch
Affiliation:
Retina Foundation of the Southwest, Dallas, and Department of Ophthalmology, University of Texas Southwestern Medical School, Dallas
Donald C. Hood
Affiliation:
Department of Psychology, Columbia University, New York.

Abstract

In the human eye, domination of the electroretinogram (ERG) by the b−wave and other postreceptor components ordinarily obscures all but the first few milliseconds of the rod photoreceptor response to a stimulating flash. However, recovery of the rod response after a bright test flash can be analyzed using a paired-flash paradigm in which the test flash, presented at time zero, is followed at time t by a bright probe flash that rapidly saturates the rods (Birch et al., 1995). In ERG experiments on normal subjects, the hypothesis that a similar method can be used to obtain the full time course of the rod response to test flashes of subsaturating intensity was tested. Rod-only responses to probe flashes presented at varying times t after the test flash were used to derive a family of amplitudes A(t) that represented the putative rod response to the test flash. These rod-only responses to the probe flash were obtained by computational subtraction of the cone-mediated component of each probe flash response. With relatively weak test flashes (11–15 scot-td-s), the time course of the rod response to the test flash derived in this manner was consistent with a four-stage impulse response function of time-to-peak ≃170 ms. A(170), the amplitude of the derived response at 170 ms, increased with test flash intensity (Itest) to a maximum value Amo and exhibited a dependence on Itest given approximately by the relation, A(170)/Amo = 1 - exp(-kItest), where k = 0.092 (scot-td-s)−1. In steady background light, the falling (i.e. recovery) phase of the derived response began earlier, and the sensitivity parameter k was reduced several-fold from its dark-adapted value. As the sensitivity, kinetics, and light-adaptation properties of the derived response correspond closely with those of photocurrent flash responses previously obtained from isolated rods in vitro, it was concluded that the response derived here from the human ERG approximates the course of the massed in vivo rod response to a test flash.

Type
Research Articles
Copyright
Copyright © Cambridge University Press 1997

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References

Baylor, D.A. (1987). Photoreceplor signals and vision. Proctor Lecture. Investigative Ophthalmology and Visual Science 28, 3449.Google ScholarPubMed
Baylor, D.A., Hodgkin, A.L. & Lamb, T.D. (1974). The electrical response of turtle cones to flashes and steps of light. Journal of Physiology 242, 685727.CrossRefGoogle ScholarPubMed
Baylor, D.A., Lamb, T.D. & Yau, K.-W. (1979). The membrane current of single rod outer segments. Journal of Physiology 288, 589611.CrossRefGoogle ScholarPubMed
Baylor, D.A., Nunn, B.J. & Schnapp, J.L. (1984). The photocurrent, noise and spectral sensitivity of rods of the monkey Macaca fascicularis. Journal of Physiology 357, 575607.CrossRefGoogle ScholarPubMed
Birch, D.G., Hood, D.C., Nusinowitz, S. & Pepperberg, D.R. (1995). Abnormal activation and inactivation mechanisms of rod transduction in patients with autosomal dominant retinitis pigmentosa and the pro-23-his mutation. Investigative Ophthalmology and Visual Science 36, 16031614.Google ScholarPubMed
Breton, M.E. & Montzka, O.P. (1992). Empiric limits of rod photocurrent component underlying a−wave response in the electroretinogram. Documenta Ophthalmologies 79, 337361.CrossRefGoogle ScholarPubMed
Breton, M.E., Schueller, A.W., Lamb, T.D. & Pugh, E.N. Jr., (1994). Analysis of ERG a−wave amplification and kinetics in terms of the G-protein cascade of phototransduction. Investigative Ophthalmology and Visual Science 35, 295309.Google ScholarPubMed
Brown, K.T. & Wiesel, T.N. (1961). Localization of origins of electroretinogram components by intraretinal recording in the intact cat eye. Journal of Physiology 158, 257280.CrossRefGoogle ScholarPubMed
Bush, R.A. & Sieving, P.A. (1994). A proximal retinal component in the primate photopic ERG a−wave. Investigative Ophthalmology and Visual Science 35, 635645.Google ScholarPubMed
Chen, J., Making, C.L., Peachey, N.S., Baylor, D.A. & Simon, M.I. (1995). Mechanisms of rhodopsin inactivation in vivo as revealed by a COOH-terminal truncation mutant. Science 267, 374377.CrossRefGoogle ScholarPubMed
Cideciyan, A.V. & Jacobson, S.G. (1993). Negative electroretinograms in retinitis pigmentosa. Investigative Ophthalmology and Visual Science 34, 32533263.Google ScholarPubMed
Cideciyan, A.V. & Jacobson, S.G. (1996). An alternative phototransduction model for human rod and cone ERG a−waves: Normal parameters and variation with age. Vision Research 36, 26092621.CrossRefGoogle ScholarPubMed
Cornwall, M.C., Ripps, H., Chappell, R.L. & Jones, G.J. (1989). Membrane current responses of skate photoreceptors. Journal of General Physiology 94, 633647.CrossRefGoogle ScholarPubMed
Dowling, J.E. (1987). The Retina: An Approachable Part of the Brain, pp. 164186. Cambridge, Massachusets: Belknap Press of Harvard University Press.Google Scholar
Fain, G.L., Lamb, T.D., Matthews, H.R. & Murphy, R.L.W. (1989). Cytoplasmic calcium as the messenger for light adaptation in salamander rods. Journal of Physiology 416, 215243.CrossRefGoogle ScholarPubMed
Forti, S., Menini, A., Rispoli, G. & Torre, V. (1989). Kinetics of photo-transduction in retinal rods of the newt Trituras cristatus. Journal of Physiology 419, 265295.CrossRefGoogle Scholar
Frishman, L.J. & Sieving, P.A. (1995). Evidence for two sites of adaptation affecting the dark-adapted ERG of cats and primates. Vision Research 35, 435442.CrossRefGoogle ScholarPubMed
Goto, Y., Peachey, N.S., Ziroli, N.E., Seiple, W.H., Gryczan, C., Pepperberg, D.R. & Naash, M.I. (1996). Rod phototransduction in transgenic mice expressing a mutant opsin gene. Journal of the Optical Society of America A 13, 577585.Google ScholarPubMed
Granit, R. (1933). The components of the retinal action potential in mammals and their relation to the discharge in the optic nerve. Journal of Physiology 77, 207239.CrossRefGoogle Scholar
Gray-Keller, M.P. & Detwiler, P.B. (1994). The calcium feedback signal in the phototransduction cascade of vertebrate rods. Neuron 13, 849861.CrossRefGoogle ScholarPubMed
Heynen, H. & Van Norren, D. (1985 a). Origin of the electroretinogram in the intact macaque eye. I. Principal component analysis. Vision Research 25, 697707.CrossRefGoogle ScholarPubMed
Heynen, H. & Van Norren, D. (1985 b). Origin of the electroretinogram in the intact macaque eye. II. Current source-density analysis. Vision Research 25, 709715.CrossRefGoogle ScholarPubMed
Hood, D.C. & Birch, D.G. (1990 a). A quantitative measure of the electrical activity of human rod photoreceptors using electroretinography. Visual Neuroscience 5, 379387.CrossRefGoogle ScholarPubMed
Hood, D.C. & Birch, D.G. (1990 b). The a−wave of the human electroretinogram and rod receptor function. Investigative Ophthalmology and Visual Science 31, 20702081.Google ScholarPubMed
Hood, D.C. & Birch, D.G. (1993). Light adaptation of human rod receptors: The leading edge of the human a−wave and models of rod receptor activity. Vision Research 33, 16051618.CrossRefGoogle Scholar
Hood, D.C. & Birch, D.G. (1994). Rod phototransduction in retinitis pigmentosa: Estimation and interpretation of parameters derived from the rod a−wave. Investigative Ophthalmology and Visual Science 35, 29482961.Google ScholarPubMed
Hood, D.C. & Birch, D.G. (1996 a). b−wave of the scotopic (rod) electroretinogram as a measure of the activity of human on-bipolar cells. Journal of the Optical Society of America A 13, 623633.CrossRefGoogle Scholar
Hood, D.C. & Birch, D.G. (1996 b). Phototransduction in human cones measured using the a−wave of the ERG. Vision Research 35, 28012810.CrossRefGoogle Scholar
Hood, D.C., Birch, D.G. & Pepperberg, D.R. (1996). The trailing edge of the photoresponse from human cones derived using a two-flash ERG paradigm. In Vision Science and Its Applications, Vol. 1, pp. 6467. Washington, DC: 1996 OSA Technical Digest Series (Optical Society of America).Google Scholar
Kraft, T.W., Schneeweis, D.M. & Schnapp, J.L. (1993). Visual transduction in human rod photoreceptors. Journal of Physiology 464, 747765.CrossRefGoogle ScholarPubMed
Lamb, T.D., Mcnaughton, P.A. & Yau, K.-W. (1981). Spatial spread of activation and background desensitization in toad rod outer segments. Journal of Physiology 319, 463496.CrossRefGoogle ScholarPubMed
Lyubarsky, A.L. & Pugh, E.N. Jr., (1996). Recovery phase of the murine rod photoresponse reconstructed from electroretinographic recordings. Journal of Neuroscience 16, 563571.CrossRefGoogle ScholarPubMed
Matthews, H.R. (1991). Incorporation of chelator into guinea-pig rods shows that calcium mediates mammalian photoreceptor light adaptation. Journal of Physiology 436, 93105.CrossRefGoogle ScholarPubMed
McNaughton, P.A. (1990). Light response of vertebrate photoreceptors. Physiological Reviews 70, 847883.CrossRefGoogle ScholarPubMed
Nakatani, K., Tamura, T. & Yau, K.-W. (1991). Light adaptation in retinal rods of the rabbit and two other nonprimate mammals. Journal of General Physiology 97, 413435.CrossRefGoogle ScholarPubMed
Ogden, T.E. (1994). Clinical electroretinography. In Retina, Vol. 1, second edition, ed. Ryan, S.J., pp. 321332. St. Louis, Missouri: Mosby.Google Scholar
Penn, R.D. & Hagins, W.A. (1969). Signal transmission along retinal rods and the origin of the electroretinographic a−wave. Nature 223, 201205.CrossRefGoogle ScholarPubMed
Pepperberg, D.R., Birch, D.G., Hofmann, K.P. & Hood, D.C. (1996 a). Recovery kinetics of human rod phototransduction inferred from the two-branched a−wave saturation function. Journal of the Optical Society of America A 13, 586600.CrossRefGoogle ScholarPubMed
Pepperberg, D.R., Birch, D.G. & Hood, D.C. (1996 b) Flash responses of human rods in vivo derived from paired-flash ERGs. Investigative Ophthalmology and Visual Science (Abstracts) 37, S5.Google Scholar
Pepperberg, D.R., Cornwall, M.C., Kahlert, M., Hofmann, K.P., Jin, J., Jones, G.J. & Ripps, H. (1992). Light-dependent delay in the falling phase of the retinal rod photoresponse. Visual Neuroscience 8, 918.CrossRefGoogle ScholarPubMed
Pepperberg, D.R., Jin, J. & Jones, G.J. (1994). Modulation of transduction gain in light adaptation of retinal rods. Visual Neuroscience 11, 5362.CrossRefGoogle ScholarPubMed
Robinson, D.W., Ratto, G.M., Lagnado, L. & Mcnaughton, P.A. (1993). Temperature dependence of the light response in rat rods. Journal of Physiology 462, 465481.CrossRefGoogle ScholarPubMed
Robson, J.G. & Frishman, L.J. (1995). Response linearity and kinetics of the cat retina: The bipolar cell component of the dark-adapted electroretinogram. Visual Neuroscience 12, 837850.CrossRefGoogle ScholarPubMed
Robson, J.G. & Frishman, L.J. (1996). Photoreceptor and bipolar-cell contributions to the cat electroretinogram: A kinetic model for the early part of the flash response. Journal of the Optical Society of America A 13, 613622.CrossRefGoogle Scholar
Sillman, A.J., Ito, H. & Tomita, T. (1969). Studies on the mass receptor potential of the isolated frog retina. I. General properties of the response. Vision Research 9, 14351442.CrossRefGoogle ScholarPubMed
Steinberg, R.H., Frishman, L.J. & Sieving, P.A. (1991). Negative components of the electroretinogram from proximal retina and photoreceptor. In Progress in Retinal Research, Vol. 10, eds. Osborne, N.N. & Chader, G.J., pp. 121160. Oxford: Pergamon.Google Scholar
Tamura, T., Nakatani, K. & Yau, K.-W. (1989). Light adaptation in cat retinal rods. Science 245, 755758.CrossRefGoogle ScholarPubMed
Tamura, T., Nakatani, K. & Yau, K.-W. (1991). Calcium feedback and sensitivity regulation in primate rods. Journal of General Physiology 98, 95130.CrossRefGoogle ScholarPubMed
Torre, V., Matthews, H.R. & Lamb, T.D. (1986). Role of calcium in regulating the cyclic GMP cascade of phototransduction in retinal rods. Proceedings of the National Academy of Sciences of the U.S.A. 83, 71097113.CrossRefGoogle ScholarPubMed