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Flicker assessment of rod and cone function in a model of retinal degeneration

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Abstract

Critical flicker frequency (CFF) is the lowest frequency for which a flickering light is indistinguishable from a non-flickering light of the same mean luminance. CFF is related to light intensity, with cone photoreceptors capable of achieving higher CFF than rods. A contemporaneous measure of rod and cone function can facilitate characterization of a retinal degeneration. We used sinusoidal flicker ERG to obtain CFF values, over a wide range of light intensities, in RCS dystrophic (RCS-p+) and wild type rats. Recordings were made at PN23, PN44, and PN64. The CFF curve in control animals increased in proportion to the log of stimulus intensity, with a gentle slope over the lowest 4 log-unit intensity range. The slope of the CFF curve dramatically increased for higher intensities, indicating a rod-cone break. In the RCS rats the rod driven CFF was significantly lower in amplitude compared to normal rats at the earliest age tested (PN23). By PN64 the rod driven CFF was immeasurable in the RCS rats. The amplitude of the cone driven CFF approached normal values at PN23, but was greatly reduced by PN44. By PN64 the entire CFF function was greatly depressed and there was no longer a discernable rod–cone break. These CFF/ERG data show that RCS rats exhibit significant early degeneration of the rods, followed soon after by degeneration of the cones. Using this approach, rod and cone function can be independently accessed using flicker ERG by testing at a few select intensities.

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References

  1. Boughman JA, Conneally PM, Nance WE (1980) Population genetic studies of retinitis pigmentosa. Am J Hum Genet 32:223–235

    PubMed  CAS  Google Scholar 

  2. Bourla DH, Young TA (2006) Age-related macular degeneration: a practical approach to a challenging disease. J Am Geriatr Soc 54:1130–1135

    Article  PubMed  Google Scholar 

  3. Hartong DT, Berson EL, Dryja TP (2006) Retinitis pigmentosa. Lancet 368:1795–1809

    Article  PubMed  CAS  Google Scholar 

  4. de Jong PT (2006) Age-related macular degeneration. N Engl J Med 355:1474–1485

    Article  PubMed  Google Scholar 

  5. Chader GJ (2002) Animal models in research on retinal degenerations: past progress and future hope. Vision Res 42:393–399

    Article  PubMed  Google Scholar 

  6. Delyfer MN, Leveillard T, Mohand-Said S, Hicks D, Picaud S, Sahel JA (2004) Inherited retinal degenerations: therapeutic prospects. Biol Cell 96:261–269

    Article  PubMed  CAS  Google Scholar 

  7. Pinilla I, Lund RD, Sauve Y (2004) Contribution of rod and cone pathways to the dark-adapted electroretinogram (ERG) b-wave following retinal degeneration in RCS rats. Vision Res 44:2467–2474

    Article  PubMed  CAS  Google Scholar 

  8. Pinilla I, Lund RD, Sauve Y (2005) Cone function studied with flicker electroretinogram during progressive retinal degeneration in RCS rats. Exp Eye Res 80:51–59

    Article  PubMed  CAS  Google Scholar 

  9. Neitz J, Jacobs GH (1986) Reexamination of spectral mechanisms in the rat (Rattus norvegicus). J Comp Psychol 100:21–29

    Article  PubMed  CAS  Google Scholar 

  10. Dowling JE, Sidman RL (1962) Inherited retinal dystrophy in the rat. J Cell Biol 14:73–109

    Article  PubMed  CAS  Google Scholar 

  11. Arnhold S, Heiduschka P, Klein H, Absenger Y, Basnaoglu S, Kreppel F, Henke-Fahle S, Kochanek S, Bartz-Schmidt KU, Addicks K, Schraermeyer U (2006) Adenovirally Transduced bone marrow stromal cells differentiate into pigment epithelial cells and induce rescue effects in RCS rats. Invest Ophthalmol Vis Sci 47:4121–4129

    Article  PubMed  Google Scholar 

  12. Corwin TR, Dunlap WP (1987) The shape of the high frequency flicker sensitivity curve. Vision Res 27:2119–2123

    Article  PubMed  CAS  Google Scholar 

  13. Bush RA, Sieving PA (1996) Inner retinal contributions to the primate photopic fast flicker electroretinogram. J Opt Soc Am A Opt Image Sci Vis 13:557–565

    Article  PubMed  CAS  Google Scholar 

  14. Kondo M, Sieving PA (2001) Primate photopic sine-wave flicker ERG: vector modeling analysis of component origins using glutamate analogs. Invest Ophthalmol Vis Sci 42:305–312

    PubMed  CAS  Google Scholar 

  15. Krishna VR, Alexander KR, Peachey NS (2002) Temporal properties of the mouse cone electroretinogram. J Neurophysiol 87:42–48

    PubMed  Google Scholar 

  16. Robson JG, Frishman LJ (1995) Response linearity and kinetics of the cat retina: the bipolar cell component of the dark-adapted electroretinogram. Vis Neurosci 12:837–850

    PubMed  CAS  Google Scholar 

  17. Hood DC, Birch DG (1996) Beta wave of the scotopic (rod) electroretinogram as a measure of the activity of human on-bipolar cells. J Opt Soc Am A Opt Image Sci Vis 13:623–633

    PubMed  CAS  Google Scholar 

  18. Lee BB, Martin PR, Valberg A (1989) Sensitivity of macaque retinal ganglion cells to chromatic and luminance flicker. J Physiol 414:223–243

    PubMed  CAS  Google Scholar 

  19. Sokol S, Riggs LA (1971) Electrical and psychophysical responses of the human visual system to periodic variation of luminance. Invest Ophthalmol 10:171–180

    PubMed  CAS  Google Scholar 

  20. Van Der Tweel L (1964) Relation between psychophysics and electrophysiology of flicker. Doc Ophthalmol 18:287–304

    Article  Google Scholar 

  21. Coile DC, Pollitz CH, Smith JC (1989) Behavioral determination of critical flicker fusion in dogs. Physiol Behav 45:1087–1092

    Article  PubMed  CAS  Google Scholar 

  22. Hecht S, Smith EL (1936) Intermittent stimulation by light. VI. Area and the relation between critical frequency and intensity. J Gen Physiol 19:979–991

    Article  Google Scholar 

  23. Dodt E, Wirth A (1953) Differentiation between rods and cones by flicker electroretinography in pigeon and guinea pig. Acta Physiol Scand 30:80–89

    PubMed  CAS  Google Scholar 

  24. Lyubarsky AL, Pugh EN Jr (1996) Recovery phase of the murine rod photoresponse reconstructed from electroretinographic recordings. J Neurosci 16:563–571

    PubMed  CAS  Google Scholar 

  25. Sharpe LT, Stockman A, MacLeod DI (1989) Rod flicker perception: scotopic duality, phase lags and destructive interference. Vision Res 29:1539–1559

    Article  PubMed  CAS  Google Scholar 

  26. Dodt E, Echte K (1961) Dark and light adaptation in pigmented and white rat as measured by electroretinogram threshold. J Neurophysiol 24:427–445

    PubMed  CAS  Google Scholar 

  27. Dowling JE (1967) Visual adaptation: its mechanism. Science 157:584–585

    PubMed  CAS  Google Scholar 

  28. Green DG (1971) Light adaptation in the rat retina: evidence for two receptor mechanisms. Science 174:598–600

    Article  PubMed  CAS  Google Scholar 

  29. Noell WK (1963) Cellular physiology of the retina. J Opt Soc Am 53:36–48

    Google Scholar 

  30. LaVail MM, Sidman RL, Gerhardt CO (1975) Congenic strains of RCS rats with inherited retinal dystrophy. J Hered 66:242–244

    PubMed  CAS  Google Scholar 

  31. LaVail MM, Battelle BA (1975) Influence of eye pigmentation and light deprivation on inherited retinal dystrophy in the rat. Exp Eye Res 21:167–192

    Article  PubMed  CAS  Google Scholar 

  32. Bush RA, Hawks KW, Sieving PA (1995) Preservation of inner retinal responses in the aged Royal College of Surgeons rat. Evidence against glutamate excitotoxicity in photoreceptor degeneration. Invest Ophthalmol Vis Sci 36:2054–2062

    PubMed  CAS  Google Scholar 

  33. Birch DG, Hood DC, Nusinowitz S, Pepperberg DR (1995) Abnormal activation and inactivation mechanisms of rod transduction in patients with autosomal dominant retinitis pigmentosa and the pro-23-his mutation. Invest Ophthalmol Vis Sci 36:1603–1614

    PubMed  CAS  Google Scholar 

  34. Cuenca N, Pinilla I, Sauve Y, Lund R (2005) Early changes in synaptic connectivity following progressive photoreceptor degeneration in RCS rats. Eur J Neurosci 22:1057–1072

    Article  PubMed  Google Scholar 

  35. Hankins M, Ikeda H (1994) Early abnormalities of retinal dopamine pathways in rats with hereditary retinal dystrophy. Doc Ophthalmol 86:325–334

    Article  PubMed  CAS  Google Scholar 

  36. Perlman I (1978) Kinetics of bleaching and regeneration of rhodopsin in abnormal (RCS) and normal albino rats in vivo. J Physiol 278:141–159

    PubMed  CAS  Google Scholar 

  37. Pinilla I, Lund RD, Sauve Y (2005) Enhanced cone dysfunction in rats homozygous for the P23H rhodopsin mutation. Neurosci Lett 382:16–21

    Article  PubMed  CAS  Google Scholar 

  38. Nusinowitz S, Ridder WH, Ramirez J (2007) Temporal response properties of the primary and secondary rodsignaling pathways in normal and Gnat2 mutant mice. Exp Eye Res 84:1104–1114.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors wish to thank Michael S. Loop for helpful discussions and critical reading of the manuscript.

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Authors and Affiliations

  1. Department of Vision Sciences, University of Alabama at Birmingham, 924 18th Street South, Worrell Building, Birmingham, AL, 35294-4390, USA

    Glen R. Rubin & Timothy W. Kraft

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  1. Glen R. Rubin
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  2. Timothy W. Kraft
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Correspondence to Timothy W. Kraft.

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Rubin, G.R., Kraft, T.W. Flicker assessment of rod and cone function in a model of retinal degeneration. Doc Ophthalmol 115, 165–172 (2007). https://doi.org/10.1007/s10633-007-9066-9

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  • DOI: https://doi.org/10.1007/s10633-007-9066-9

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