Skip to main content
Erschienen in: Documenta Ophthalmologica 3/2007

01.11.2007 | Original Research paper

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

verfasst von: Glen R. Rubin, Timothy W. Kraft

Erschienen in: Documenta Ophthalmologica | Ausgabe 3/2007

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat Boughman JA, Conneally PM, Nance WE (1980) Population genetic studies of retinitis pigmentosa. Am J Hum Genet 32:223–235PubMed Boughman JA, Conneally PM, Nance WE (1980) Population genetic studies of retinitis pigmentosa. Am J Hum Genet 32:223–235PubMed
2.
Zurück zum Zitat Bourla DH, Young TA (2006) Age-related macular degeneration: a practical approach to a challenging disease. J Am Geriatr Soc 54:1130–1135PubMedCrossRef Bourla DH, Young TA (2006) Age-related macular degeneration: a practical approach to a challenging disease. J Am Geriatr Soc 54:1130–1135PubMedCrossRef
5.
Zurück zum Zitat Chader GJ (2002) Animal models in research on retinal degenerations: past progress and future hope. Vision Res 42:393–399PubMedCrossRef Chader GJ (2002) Animal models in research on retinal degenerations: past progress and future hope. Vision Res 42:393–399PubMedCrossRef
6.
Zurück zum Zitat Delyfer MN, Leveillard T, Mohand-Said S, Hicks D, Picaud S, Sahel JA (2004) Inherited retinal degenerations: therapeutic prospects. Biol Cell 96:261–269PubMedCrossRef Delyfer MN, Leveillard T, Mohand-Said S, Hicks D, Picaud S, Sahel JA (2004) Inherited retinal degenerations: therapeutic prospects. Biol Cell 96:261–269PubMedCrossRef
7.
Zurück zum Zitat 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 44:2467–2474PubMedCrossRef 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 44:2467–2474PubMedCrossRef
8.
Zurück zum Zitat Pinilla I, Lund RD, Sauve Y (2005) Cone function studied with flicker electroretinogram during progressive retinal degeneration in RCS rats. Exp Eye Res 80:51–59PubMedCrossRef Pinilla I, Lund RD, Sauve Y (2005) Cone function studied with flicker electroretinogram during progressive retinal degeneration in RCS rats. Exp Eye Res 80:51–59PubMedCrossRef
9.
Zurück zum Zitat Neitz J, Jacobs GH (1986) Reexamination of spectral mechanisms in the rat (Rattus norvegicus). J Comp Psychol 100:21–29PubMedCrossRef Neitz J, Jacobs GH (1986) Reexamination of spectral mechanisms in the rat (Rattus norvegicus). J Comp Psychol 100:21–29PubMedCrossRef
10.
11.
Zurück zum Zitat 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 47:4121–4129PubMedCrossRef 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 47:4121–4129PubMedCrossRef
12.
Zurück zum Zitat Corwin TR, Dunlap WP (1987) The shape of the high frequency flicker sensitivity curve. Vision Res 27:2119–2123PubMedCrossRef Corwin TR, Dunlap WP (1987) The shape of the high frequency flicker sensitivity curve. Vision Res 27:2119–2123PubMedCrossRef
13.
Zurück zum Zitat Bush RA, Sieving PA (1996) Inner retinal contributions to the primate photopic fast flicker electroretinogram. J Opt Soc Am A Opt Image Sci Vis 13:557–565PubMedCrossRef Bush RA, Sieving PA (1996) Inner retinal contributions to the primate photopic fast flicker electroretinogram. J Opt Soc Am A Opt Image Sci Vis 13:557–565PubMedCrossRef
14.
Zurück zum Zitat Kondo M, Sieving PA (2001) Primate photopic sine-wave flicker ERG: vector modeling analysis of component origins using glutamate analogs. Invest Ophthalmol Vis Sci 42:305–312PubMed Kondo M, Sieving PA (2001) Primate photopic sine-wave flicker ERG: vector modeling analysis of component origins using glutamate analogs. Invest Ophthalmol Vis Sci 42:305–312PubMed
15.
Zurück zum Zitat Krishna VR, Alexander KR, Peachey NS (2002) Temporal properties of the mouse cone electroretinogram. J Neurophysiol 87:42–48PubMed Krishna VR, Alexander KR, Peachey NS (2002) Temporal properties of the mouse cone electroretinogram. J Neurophysiol 87:42–48PubMed
16.
Zurück zum Zitat Robson JG, Frishman LJ (1995) Response linearity and kinetics of the cat retina: the bipolar cell component of the dark-adapted electroretinogram. Vis Neurosci 12:837–850PubMed Robson JG, Frishman LJ (1995) Response linearity and kinetics of the cat retina: the bipolar cell component of the dark-adapted electroretinogram. Vis Neurosci 12:837–850PubMed
17.
Zurück zum Zitat 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 13:623–633PubMed 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 13:623–633PubMed
18.
Zurück zum Zitat Lee BB, Martin PR, Valberg A (1989) Sensitivity of macaque retinal ganglion cells to chromatic and luminance flicker. J Physiol 414:223–243PubMed Lee BB, Martin PR, Valberg A (1989) Sensitivity of macaque retinal ganglion cells to chromatic and luminance flicker. J Physiol 414:223–243PubMed
19.
Zurück zum Zitat Sokol S, Riggs LA (1971) Electrical and psychophysical responses of the human visual system to periodic variation of luminance. Invest Ophthalmol 10:171–180PubMed Sokol S, Riggs LA (1971) Electrical and psychophysical responses of the human visual system to periodic variation of luminance. Invest Ophthalmol 10:171–180PubMed
20.
Zurück zum Zitat Van Der Tweel L (1964) Relation between psychophysics and electrophysiology of flicker. Doc Ophthalmol 18:287–304CrossRef Van Der Tweel L (1964) Relation between psychophysics and electrophysiology of flicker. Doc Ophthalmol 18:287–304CrossRef
21.
Zurück zum Zitat Coile DC, Pollitz CH, Smith JC (1989) Behavioral determination of critical flicker fusion in dogs. Physiol Behav 45:1087–1092PubMedCrossRef Coile DC, Pollitz CH, Smith JC (1989) Behavioral determination of critical flicker fusion in dogs. Physiol Behav 45:1087–1092PubMedCrossRef
22.
Zurück zum Zitat Hecht S, Smith EL (1936) Intermittent stimulation by light. VI. Area and the relation between critical frequency and intensity. J Gen Physiol 19:979–991CrossRef Hecht S, Smith EL (1936) Intermittent stimulation by light. VI. Area and the relation between critical frequency and intensity. J Gen Physiol 19:979–991CrossRef
23.
Zurück zum Zitat Dodt E, Wirth A (1953) Differentiation between rods and cones by flicker electroretinography in pigeon and guinea pig. Acta Physiol Scand 30:80–89PubMed Dodt E, Wirth A (1953) Differentiation between rods and cones by flicker electroretinography in pigeon and guinea pig. Acta Physiol Scand 30:80–89PubMed
24.
Zurück zum Zitat Lyubarsky AL, Pugh EN Jr (1996) Recovery phase of the murine rod photoresponse reconstructed from electroretinographic recordings. J Neurosci 16:563–571PubMed Lyubarsky AL, Pugh EN Jr (1996) Recovery phase of the murine rod photoresponse reconstructed from electroretinographic recordings. J Neurosci 16:563–571PubMed
25.
Zurück zum Zitat Sharpe LT, Stockman A, MacLeod DI (1989) Rod flicker perception: scotopic duality, phase lags and destructive interference. Vision Res 29:1539–1559PubMedCrossRef Sharpe LT, Stockman A, MacLeod DI (1989) Rod flicker perception: scotopic duality, phase lags and destructive interference. Vision Res 29:1539–1559PubMedCrossRef
26.
Zurück zum Zitat Dodt E, Echte K (1961) Dark and light adaptation in pigmented and white rat as measured by electroretinogram threshold. J Neurophysiol 24:427–445PubMed Dodt E, Echte K (1961) Dark and light adaptation in pigmented and white rat as measured by electroretinogram threshold. J Neurophysiol 24:427–445PubMed
27.
Zurück zum Zitat Dowling JE (1967) Visual adaptation: its mechanism. Science 157:584–585PubMed Dowling JE (1967) Visual adaptation: its mechanism. Science 157:584–585PubMed
28.
Zurück zum Zitat Green DG (1971) Light adaptation in the rat retina: evidence for two receptor mechanisms. Science 174:598–600PubMedCrossRef Green DG (1971) Light adaptation in the rat retina: evidence for two receptor mechanisms. Science 174:598–600PubMedCrossRef
29.
Zurück zum Zitat Noell WK (1963) Cellular physiology of the retina. J Opt Soc Am 53:36–48 Noell WK (1963) Cellular physiology of the retina. J Opt Soc Am 53:36–48
30.
Zurück zum Zitat LaVail MM, Sidman RL, Gerhardt CO (1975) Congenic strains of RCS rats with inherited retinal dystrophy. J Hered 66:242–244PubMed LaVail MM, Sidman RL, Gerhardt CO (1975) Congenic strains of RCS rats with inherited retinal dystrophy. J Hered 66:242–244PubMed
31.
Zurück zum Zitat LaVail MM, Battelle BA (1975) Influence of eye pigmentation and light deprivation on inherited retinal dystrophy in the rat. Exp Eye Res 21:167–192PubMedCrossRef LaVail MM, Battelle BA (1975) Influence of eye pigmentation and light deprivation on inherited retinal dystrophy in the rat. Exp Eye Res 21:167–192PubMedCrossRef
32.
Zurück zum Zitat 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 36:2054–2062PubMed 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 36:2054–2062PubMed
33.
Zurück zum Zitat 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 36:1603–1614PubMed 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 36:1603–1614PubMed
34.
Zurück zum Zitat Cuenca N, Pinilla I, Sauve Y, Lund R (2005) Early changes in synaptic connectivity following progressive photoreceptor degeneration in RCS rats. Eur J Neurosci 22:1057–1072PubMedCrossRef Cuenca N, Pinilla I, Sauve Y, Lund R (2005) Early changes in synaptic connectivity following progressive photoreceptor degeneration in RCS rats. Eur J Neurosci 22:1057–1072PubMedCrossRef
35.
Zurück zum Zitat Hankins M, Ikeda H (1994) Early abnormalities of retinal dopamine pathways in rats with hereditary retinal dystrophy. Doc Ophthalmol 86:325–334PubMedCrossRef Hankins M, Ikeda H (1994) Early abnormalities of retinal dopamine pathways in rats with hereditary retinal dystrophy. Doc Ophthalmol 86:325–334PubMedCrossRef
36.
Zurück zum Zitat Perlman I (1978) Kinetics of bleaching and regeneration of rhodopsin in abnormal (RCS) and normal albino rats in vivo. J Physiol 278:141–159PubMed Perlman I (1978) Kinetics of bleaching and regeneration of rhodopsin in abnormal (RCS) and normal albino rats in vivo. J Physiol 278:141–159PubMed
37.
Zurück zum Zitat Pinilla I, Lund RD, Sauve Y (2005) Enhanced cone dysfunction in rats homozygous for the P23H rhodopsin mutation. Neurosci Lett 382:16–21PubMedCrossRef Pinilla I, Lund RD, Sauve Y (2005) Enhanced cone dysfunction in rats homozygous for the P23H rhodopsin mutation. Neurosci Lett 382:16–21PubMedCrossRef
38.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
Metadaten
Titel
Flicker assessment of rod and cone function in a model of retinal degeneration
verfasst von
Glen R. Rubin
Timothy W. Kraft
Publikationsdatum
01.11.2007
Verlag
Springer-Verlag
Erschienen in
Documenta Ophthalmologica / Ausgabe 3/2007
Print ISSN: 0012-4486
Elektronische ISSN: 1573-2622
DOI
https://doi.org/10.1007/s10633-007-9066-9

Weitere Artikel der Ausgabe 3/2007

Documenta Ophthalmologica 3/2007 Zur Ausgabe

Original Research Article

The mouse pattern electroretinogram

Neu im Fachgebiet Augenheilkunde

Update Augenheilkunde

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.