Purpose. To describe the characteristics of rod and cone functions in rat models for congenital stationary night blindness (CSNB) and retinal cone dysfunction (RCD). Methods. Rod and cone function were isolated by recording the rod-/cone-driven flicker and blue light flicker electroretinograms (ERGs). Results. During dark adaptation, the amplitudes of flicker ERGs in CSNB rats were lower than those in control rats; the responses of RCD rats were similar to control rats. During light adaptation, the amplitudes of flicker ERGs in CSNB rats were reduced; whereas the responses of RCD rats were not detected. Blue flicker ERGs were not observed in CSNB rats at lower frequencies. The cone driven critical flicker frequencies (CFFs) in control rats were 62？Hz. The rod driven CFF of RCD rats was 20？Hz; whereas the rod-/cone-driven CFF of CSNB rats both were about 25？Hz. Conclusions. The function of the rod system was damaged completely, the cones were the source of vision in CSNB rats. Rod system function is excellent in RCD rat. The rods of albinism rats are sensitive to frequencies less than 20？Hz; whereas the cones are sensitive to frequencies up to 62？Hz. 1. Introduction Inherited retinal degeneration disorder is one of the most serious diseases that cause blindness in humans. Gene mutations are expressed in photoreceptors, bipolar cells, or other part of the retina, which can cause various changes in rod and cone function. The loss of rod or cone path function or visual signal transduction results in serious eye disease in humans. However, the pathogenesis of retinal degeneration disorder is still not quite understood, and valid treatment is currently lacking. Clinically, the classification of retinal diseases mainly depends on electroretinograms (ERGs) to analyze the extent of damage to the cone and rod systems. Spontaneous generation animal models of retinal degeneration are important for studying gene mutation, protein function, and disease prevention, and cure. Congenital stationary night blindness (CSNB) is a nonprogressive retinal degeneration disease characterized by the loss of night vision with partially or completely absent rod function [1]. CSNB disease is transmitted via an autosomal recessive, autosomal dominant or X-linked mode of inheritance. Several groups have shown that the genetic heterogeneity of the X-linked CSNB (XLCSNB) is controlled by two different loci on the X chromosome. The NYX gene mutation gives rise to cCSNB (CSNB1), whereas the CACNA1F gene mutation leads to iCSNB (CSNB2) [2–7]. Retinal cone dysfunction (RCD) [8] is a retina
References
[1]
H. Ripps, “Night blindness revisited: from man to molecules. Proctor lecture,” Investigative Ophthalmology and Visual Science, vol. 23, no. 5, pp. 588–609, 1982.
[2]
C. M. Pusch, C. Zeitz, O. Brandau et al., “The complete form of X-linked congenital stationary night blindness is caused by mutations in a gene encoding a leucine-rich repeat protein,” Nature Genetics, vol. 26, no. 3, pp. 324–327, 2000.
[3]
N. T. Bech-Hansen, M. J. Naylor, T. A. Maybaum et al., “Mutations in NYX, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness,” Nature Genetics, vol. 26, no. 3, pp. 319–323, 2000.
[4]
T. M. Strom, G. Nyakatura, E. Apfelstedt-Sylla et al., “An L-type calcium-channel gene mutated in incomplete X-linked congenital stationary night blindness,” Nature Genetics, vol. 19, no. 3, pp. 260–263, 1998.
[5]
S. I. Candille, M. T. Pardue, M. A. McCall, N. S. Peachey, and R. G. Gregg, “Localization of the mouse nob (no b-wave) gene to the centromeric region of the X chromosome,” Investigative Ophthalmology and Visual Science, vol. 40, no. 11, pp. 2748–2751, 1999.
[6]
B. Chang, J. R. Heckenlively, P. R. Bayley et al., “The nob2 mouse, a null mutation in Cacna1f: anatomical and functional abnormalities in the outer retina and their consequences on ganglion cell visual responses,” Visual Neuroscience, vol. 23, no. 1, pp. 11–24, 2006.
[7]
Y. Gu, L. Wang, J. Zhou et al., “A naturally-occurring mutation in Cacna1f in a rat model of congenital stationary night blindness,” Molecular Vision, vol. 14, pp. 20–28, 2008.
[8]
Y. H. Gu, Z. M. Zhang, T. Long, L. Li, B. K. Hou, and Q. Guo, “A naturally occurring rat model of X-linked cone dystrophy,” Investigative Ophthalmology and Visual Science, vol. 44, no. 12, pp. 5321–5326, 2003.
[9]
M. D. Fischer, N. Tanimoto, S. C. Beck et al., “Structural and functional phenotyping in the cone-specific photoreceptor function loss 1 (cpfl1) mouse mutant-A model of cone dystrophies,” Advances in Experimental Medicine and Biology, vol. 664, pp. 593–599, 2010.
[10]
S. Kohl, B. Baumann, T. Rosenberg et al., “Mutations in the cone photoreceptor G-protein alpha-subunit gene GNAT2 in patients with achromatopsia,” American Jounral of Human Genetics, vol. 71, no. 2, pp. 422–425, 2002.
[11]
S. Kohl, B. Varsanyi, G. A. Antunes et al., “CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia,” European Journal of Human Genetics, vol. 13, no. 3, pp. 302–308, 2005.
[12]
B. Xie, S. Nakanishi, Q. Guo et al., “A novel middle-wavelength opsin (M-opsin) null-mutation in the retinal cone dysfunction rat,” Experimental Eye Research, vol. 91, no. 1, pp. 26–33, 2010.
[13]
Y. Goto, T. Yasuda, S. Tobimatsu, and M. Kato, “20-Hz flicker stimulus can isolate the cone function in rat retina,” Ophthalmic Research, vol. 30, no. 6, pp. 368–373, 1998.
[14]
S. H. Goldberg, T. E. Frumkes, and R. W. Nygaard, “Inhibitory influencc of unstimulatcd rods in the human rctina: evidence provided by examining cone flicker,” Science, vol. 221, no. 4606, pp. 180–182, 1983.
[15]
N. J. Coletta and A. J. Adams, “Rod-cone interaction in flicker detection,” Vision Research, vol. 24, no. 10, pp. 1333–1340, 1984.
[16]
N. S. Peachey, K. R. Alexander, D. J. Derlacki, and G. A. Fishman, “Light adaptation and the luminance-response function of the cone electroretinogram,” Documenta Ophthalmologica, vol. 79, no. 4, pp. 363–369, 1992.
[17]
M. Kondo and P. A. Sieving, “Primate photopic sine-wave flicker ERG: vector modeling analysis of component origins using glutamate analogs,” Investigative Ophthalmology and Visual Science, vol. 42, no. 1, pp. 305–312, 2001.
[18]
N. W. Khan, M. Kondo, K. T. Hiriyanna, J. A. Jamison, R. A. Bush, and P. A. Sieving, “Primate retinal signaling pathways: suppressing on-pathway activity in monkey with glutamate analogues mimics human CSNB1-NYX genetic night blindness,” Journal of Neurophysiology, vol. 93, no. 1, pp. 481–492, 2005.
[19]
V. R. Krishna, K. R. Alexander, and N. S. Peachey, “Temporal properties of the mouse cone electroretinogram,” Journal of Neurophysiology, vol. 87, no. 1, pp. 42–48, 2002.
[20]
S. Shirato, H. Maeda, G. Miura, and L. J. Frishman, “Postreceptoral contributions to the light-adapted ERG of mice lacking b-waves,” Experimental Eye Research, vol. 86, no. 6, pp. 914–928, 2008.
[21]
C. M. Cicerone, D. G. Green, and L. J. Fisher, “Cone inputs to ganglion cells in hereditary retinal degeneration,” Science, vol. 203, no. 4385, pp. 1113–1115, 1979.
[22]
I. Pinilla, R. D. Lund, and Y. Sauvé, “Cone function studied with flicker electroretinogram during progressive retinal degeneration in RCS rats,” Experimental Eye Research, vol. 80, no. 1, pp. 51–59, 2005.
[23]
G. R. Rubin and T. W. Kraft, “Flicker assessment of rod and cone function in a model of retinal degeneration,” Documenta Ophthalmologica, vol. 115, no. 3, pp. 165–172, 2007.
[24]
K. R. Alexander, G. A. Fishman, and S. Grover, “Temporal frequency deficits in the electroretinogram of the cone system in X-linked retinoschisis,” Vision Research, vol. 40, no. 20, pp. 2861–2868, 2000.
[25]
Z. Zhang, Y. Gu, L. Li, T. Long, Q. Guo, and L. Shi, “A potential spontaneous rat model of X-linked congenital stationery night blindness,” Documenta Ophthalmologica, vol. 107, no. 1, pp. 53–57, 2003.
[26]
H. Qian, M. R. Shah, K. R. Alexander, and H. Ripps, “Two distinct processes are evident in rat cone flicker ERG responses at low and high temporal frequencies,” Experimental Eye Research, vol. 87, no. 1, pp. 71–75, 2008.
[27]
B. Ekesten, P. Gouras, and M. Moschos, “Cone properties of the light-adapted murine ERG,” Documenta Ophthalmologica, vol. 97, no. 1, pp. 23–31, 1998.
[28]
J. A. Armitage, B. V. Bui, R. Gibson, and A. J. Vingrys, “Postnatal development of flicker sensitivity in guinea pigs,” Clinical and Experimental Optometry, vol. 84, no. 5, pp. 270–275, 2001.
[29]
J. D. Conner and D. I. A. MacLeod, “Rod photoreceptors detect rapid flicker,” Science, vol. 195, no. 4279, pp. 698–699, 1977.
[30]
D. H. Kelly, “Visual responses to timedependent stimuli. I. Amplitude sensitivity measurements,” Journal of Optical Society of America A, vol. 51, pp. 422–429, 1961.
[31]
S. Nusinowitz, W. H. Ridder, and J. Ramirez, “Temporal response properties of the primary and secondary rod-signaling pathways in normal and Gnat2 mutant mice,” Experimental Eye Research, vol. 84, no. 6, pp. 1104–1114, 2007.
[32]
B. Ekesten and P. Gouras, “Cone inputs to murine striate cortex,” BMC Neuroscience, vol. 9, article no. 113, 2008.
[33]
J. D. Conner, “The temporal properties of rod vision,” Journal of Physiology, vol. 332, pp. 139–155, 1982.
[34]
T. J. van den Berg and H. Spekreijse, “Interaction between rod and cone signals studied with temporal sine wave stimulation.,” Journal of the Optical Society of America, vol. 67, no. 9, pp. 1210–1217, 1977.
[35]
M. R. Shah, K. R. Alexander, H. Ripps, and H. Qian, “Characteristics of period doubling in the rat cone flicker ERG,” Experimental Eye Research, vol. 90, no. 2, pp. 196–202, 2010.
[36]
D. I. A. Macleod, “Rods cancel cones in flicker,” Nature, vol. 235, no. 5334, pp. 173–174, 1972.
[37]
G. H. Jacobs, J. A. Fenwick, and G. A. Williams, “Cone-based vision of rats for ultraviolet and visible lights,” Experimental Biology, vol. 204, no. 14, pp. 2439–2446, 2001.
