title: Differentiation of murine models of "negative ERG" by single and repetitive light stimuli.
abstract: OBJECTIVE
  Marked attenuation of the single-flash electroretinographic (ERG) b-wave in the presence of a normal-amplitude or less-attenuated a-wave is commonly referred to as the "negative ERG." The purpose of this study was to investigate whether the disparate origins of the negative ERG in three murine models can be discriminated using flickering stimuli.
  
  
  METHODS
  Three models were selected: (1) the Nyx (nob) mouse model of complete congenital stationary night blindness, (2) the oxygen-induced retinopathy (OIR) rat model of retinopathy of prematurity (ROP), and (3) the Rs1 knockout (KO) mouse model of X-linked juvenile retinoschisis. Directly after a dark-adapted, single-flash ERG luminance series, a flicker ERG frequency series (0.5-30 Hz) was performed at a fixed luminance of 0.5 log cd s/m(2). This series includes frequency ranges that are dominated by activity in (A) the rod pathways (below 5 Hz), (B) the cone ON-pathway (5-15 Hz), and (C) the cone OFF-pathway (above 15 Hz).
  
  
  RESULTS
  All three models produced markedly attenuated single-flash ERG b-waves. In the Nyx (nob) mouse, which features postsynaptic deficits in the ON-pathways, the a-wave was normal and flicker responses were attenuated in ranges A and B, but not C. The ROP rat is characterized by inner-retinal ischemia which putatively affects both ON- and OFF-bipolar cell activity; flicker responses were reduced in all ranges (A-C). Notably, the choroid supplies the photoreceptors and is thought to be relatively intact in OIR, an idea supported by the nearly normal a-wave. Finally, in the Rs1 KO mouse, which has documented abnormality of the photoreceptor-bipolar synapse affecting both ON- and OFF-pathways, the flicker responses were attenuated in all ranges (A-C). The a-wave was also attenuated, likely as a consequence to schisms in the photoreceptor layer.
  
  
  CONCLUSIONS
  Consideration of both single-flash and flickering ERG responses can discriminate the functional pathology of the negative ERG in these animal models of human disease.
authors.affiliation: Division of Ocular Neurodegeneration, Institute for Ophthalmic Research, Centre for Ophthalmology, Eberhard Karls University, Schleichstr. 4/3, 72076, Tübingen, Germany. naoyuki.tanimoto@med.uni-tuebingen.de.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tanimoto
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, 300 Longwood Avenue, Fegan 4, Boston, MA, 02115, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Akula
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, 300 Longwood Avenue, Fegan 4, Boston, MA, 02115, USA.
authors.forename: Anne B
authors.initials: AB
authors.lastname: Fulton
authors.affiliation: Institute of Human Genetics, University of Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg, 93053, Germany.
authors.forename: Bernhard H F
authors.initials: BH
authors.lastname: Weber
authors.affiliation: Division of Ocular Neurodegeneration, Institute for Ophthalmic Research, Centre for Ophthalmology, Eberhard Karls University, Schleichstr. 4/3, 72076, Tübingen, Germany.
authors.forename: Mathias W
authors.initials: MW
authors.lastname: Seeliger
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003623:Dark Adaptation; D004195:Disease Models, Animal; D004596:Electroretinography; D015785:Eye Diseases, Hereditary / Q000503:physiopathology*; D040181:Genetic Diseases, X-Linked / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009216:Myopia / Q000503:physiopathology*; D009755:Night Blindness / Q000503:physiopathology*; D010100:Oxygen / Q000633:toxicity; D010775:Photic Stimulation; D051381:Rats; D020318:Rats, Long-Evans; D012160:Retina / Q000503:physiopathology*; D051245:Retinal Bipolar Cells / Q000502:physiology; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology; D012178:Retinopathy of Prematurity / Q000139:chemically induced / Q000503:physiopathology*; D041441:Retinoschisis / Q000503:physiopathology*
chemical_list: D010100:Oxygen
keywords: Complete congenital stationary night blindness (cCSNB); Flicker; Murine model; Negative electroretinogram; Retinopathy of prematurity (ROP); X-linked juvenile retinoschisis (XLRS)