The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Electrophysiological and Histologic Evaluation of the Time Course of Retinal Degeneration in the rd10 Mouse Model of Retinitis Pigmentosa

  • Jae, Seol A (Department of Physiology, Chungbuk National University School of Medicine) ;
  • Ahn, Kun No (Department of Physiology, Chungbuk National University School of Medicine) ;
  • Kim, Ji Young (Department of Anatomy, Chungbuk National University School of Medicine) ;
  • Seo, Je Hoon (Department of Anatomy, Chungbuk National University School of Medicine) ;
  • Kim, Hyong Kyu (Department of Microbiology, Chungbuk National University School of Medicine) ;
  • Goo, Yong Sook (Department of Physiology, Chungbuk National University School of Medicine)
  • Received : 2012.11.09
  • Accepted : 2013.05.07
  • Published : 2013.06.30
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Abstract

Among several animal models of retinitis pigmentosa (RP), the more recently developed rd10 mouse with later onset and slower rate of retinal degeneration than rd1 mouse is a more suitable model for testing therapeutic modalities. We therefore investigated the time course of retinal degeneration in rd10 mice before adopting this model in our interventional studies. Electroretinogram (ERG) recordings were carried out in postnatal weeks (PW) 3~5 rd10 (n=23) and wild-type (wt) mice (n=26). We compared the amplitude and implicit time of the b-wave of ERG records from wt and rd10 mice. Our results showed that b-wave amplitudes in rd10 mice were significantly lower and the implicit time of b-waves in rd10 mice were also significantly slower than that in wt mice ($20{\sim}160{\mu}V$ vs. $350{\sim}480{\mu}V$; 55~75 ms vs. 100~150 ms: p<0.001) through PW3 to PW5. The most drastic changes in ERG amplitudes and latencies were observed during PW3 to PW4. In multichannel recording of rd10 retina in PW2 to PW4.5, we found no significant difference in mean spike frequency, but the frequency of power spectral peak of local field potential at PW3 and PW3.5 is significantly different among other age groups (p<0.05). Histologic examination of rd10 retinae showed significant decrease in thickness of the outer nuclear layer at PW3. TUNEL positive cells were most frequently observed at PW3. From these data, we confirm that in the rd10 mouse, the most precipitous retinal degeneration occurs between PW3~PW4 and that photoreceptor degeneration is complete by PW5.

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References

  1. Pagon RA. Retinitis pigmentosa. Surv Ophthalmol. 1988;33: 137-177. https://doi.org/10.1016/0039-6257(88)90085-9
  2. Pagon RA, Daiger SP. Retinitis pigmentosa Overview. In: GeneReviews. Seattle: University of Washington; 2000.
  3. Chang B, Hawes NL, Hurd RE, Davisson MT, Nusinowitz S, Heckenlively JR. Retinal degeneration mutants in the mouse. Vision Res. 2002;42:517-525. https://doi.org/10.1016/S0042-6989(01)00146-8
  4. Chang B, Hawes NL, Pardue MT, German AM, Hurd RE, Davisson MT, Nusinowitz S, Rengarajan K, Boyd AP, Sidney SS, Phillips MJ, Stewart RE, Chaudhury R, Nickerson JM, Heckenlively JR, Boatright JH. Two mouse retinal degenerations caused by missense mutations in the beta-subunit of rod cGMP phosphodiesterase gene. Vision Res. 2007;47: 624-633. https://doi.org/10.1016/j.visres.2006.11.020
  5. Baehr W, Frederick JM. Naturally occurring animal models with outer retina phenotypes. Vision Res. 2009;49:2636-2652. https://doi.org/10.1016/j.visres.2009.04.008
  6. Goo YS, Ye JH, Lee S, Nam Y, Ryu SB, Kim KH. Retinal ganglion cell responses to voltage and current stimulation in wild-type and rd1 mouse retinas. J Neural Eng. 2011;8:035003. https://doi.org/10.1088/1741-2560/8/3/035003
  7. Ryu SB, Ye JH, Goo YS, Kim CH, Kim KH. Decoding of temporal visual information from electrically evoked retinal ganglion cell activities in photoreceptor-degenerated retinas. Invest Ophthalmol Vis Sci. 2011;52:6271-6278. https://doi.org/10.1167/iovs.11-7597
  8. Ryu SB, Ye JH, Goo YS, Kim CH, Kim KH. Temporal response properties of retinal ganglion cells in rd1 mice evoked by amplitude-modulated electrical pulse trains. Invest Ophthalmol Vis Sci. 2010;51:6762-6769. https://doi.org/10.1167/iovs.10-5577
  9. Slatter DH. Fundamentals of veterinary ophthalmology. 3rd ed. Philadelphia: Saunders; 2001. p.419-456.
  10. Armington JC, Bloom MB. Relations between the amplitudes of spontaneous saccades and visual responses. J Opt Soc Am. 1974;64:1263-1271. https://doi.org/10.1364/JOSA.64.001263
  11. Penn RD, Hagins WA. Signal transmission along retinal rods and the origin of the electroretinographic a-wave. Nature. 1969;223:201-204. https://doi.org/10.1038/223201a0
  12. Miller RF, Dowling JE. Intracellular responses of the Müller (glial) cells of mudpuppy retina: their relation to b-wave of the electroretinogram. J Neurophysiol. 1970;33:323-341. https://doi.org/10.1152/jn.1970.33.3.323
  13. Stockton RA, Slaughter MM. B-wave of the electroretinogram. A reflection of ON bipolar cell activity. J Gen Physiol. 1989;93:101-122. https://doi.org/10.1085/jgp.93.1.101
  14. Xu X, Karwoski CJ. Current source density analysis of retinal field potentials. II. Pharmacological analysis of the b-wave and M-wave. J Neurophysiol. 1994;72:96-105. https://doi.org/10.1152/jn.1994.72.1.96
  15. Shiells RA, Falk G. Contribution of rod, on-bipolar, and horizontal cell light responses to the ERG of dogfish retina. Vis Neurosci. 1999;16:503-511.
  16. Robson JG, Frishman LJ. Response linearity and kinetics of the cat retina: the bipolar cell component of the dark-adapted electroretinogram. Vis Neurosci. 1995;12:837-850. https://doi.org/10.1017/S0952523800009408
  17. Pugh EN, JR, Falsini B, Lyurbarsky A. The origin of the major rod- and cone-driven components of the rodent electroretinogram and the effects of age and light-rearing history on the magnitude of these components. In Photostasis and Related Phenomena. New York: Plenum Press; 1998. p.128.
  18. Stett A, Barth W, Haemmerle H, Weiss S, Zrenner E. Electrical multisite stimulation of the isolated chicken retina. Vision Res. 2000;40:1785-1795. https://doi.org/10.1016/S0042-6989(00)00005-5
  19. Hayes MH. Statistical digital signal processing and modeling. New York: John Wiley & Sons; 1996.
  20. LaVail MM, Matthes MT, Yasumura D, Steinberg RH. Variability in rate of cone degeneration in the retinal degeneration (rd/rd) mouse. Exp Eye Res. 1997;65:45-50. https://doi.org/10.1006/exer.1997.0308
  21. Strettoi E, Porciatti V, Falsini B, Pignatelli V, Rossi C. Morphological and functional abnormalities in the inner retina of the rd/rd mouse. J Neurosci. 2002;22:5492-5504.
  22. Strettoi E, Pignatelli V, Rossi C, Porciatti V, Falsini B. Remodeling of second-order neurons in the retina of rd/rd mutant mice. Vision Res. 2003;43:867-877. https://doi.org/10.1016/S0042-6989(02)00594-1
  23. Lin B, Masland RH, Strettoi E. Remodeling of cone photoreceptor cells after rod degeneration in rd mice. Exp Eye Res. 2009;88:589-599. https://doi.org/10.1016/j.exer.2008.11.022
  24. Chen M, Wang K, Lin B. Development and degeneration of cone bipolar cells are independent of cone photoreceptors in a mouse model of retinitis pigmentosa. PLoS One. 2012;7:e44036. https://doi.org/10.1371/journal.pone.0044036
  25. Gargini C, Terzibasi E, Mazzoni F, Strettoi E. Retinal organization in the retinal degeneration 10 (rd10) mutant mouse: a morphological and ERG study. J Comp Neurol. 2007;500: 222-238. https://doi.org/10.1002/cne.21144
  26. Lyubarsky AL, Daniele LL, Pugh EN Jr. From candelas to photoisomerizations in the mouse eye by rhodopsin bleaching in situ and the light-rearing dependence of the major components of the mouse ERG. Vision Res. 2004;44:3235-3251. https://doi.org/10.1016/j.visres.2004.09.019
  27. Barhoum R, Martinez-Navarrete G, Corrochano S, Germain F, Fernandez-Sanchez L, de la Rosa EJ, de la Villa P, Cuenca N. Functional and structural modifications during retinal degeneration in the rd10 mouse. Neuroscience. 2008;155:698-713. https://doi.org/10.1016/j.neuroscience.2008.06.042
  28. Ye JH, Goo YS. The slow wave component of retinal activity in rd/rd mice recorded with a multi-electrode array. Physiol Meas. 2007;28:1079-1088. https://doi.org/10.1088/0967-3334/28/9/009
  29. Margolis DJ, Newkirk G, Euler T, Detwiler PB. Functional stability of retinal ganglion cells after degeneration-induced changes in synaptic input. J Neurosci. 2008;28:6526-6536. https://doi.org/10.1523/JNEUROSCI.1533-08.2008

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