Pharmacological dissection of multifocal electroretinograms of rabbits with Pro347Leu rhodopsin mutation.
OBJECTIVE
To determine whether photoreceptor degeneration in transgenic (Tg) rabbits carrying the Pro347Leu rhodopsin mutation alters the neural activity of the middle and inner retinal neurons.


METHODS
Multifocal electroretinograms (mfERGs) were recorded from eight 12-week-old Tg rabbits both before and after intravitreal injection of the following: tetrodotoxin citrate (TTX), N-methyl-DL: -aspartic acid (NMDA), 2-amino-4-phosphonobutyric acid (APB), and cis-2,3-piperidine-dicarboxylic acid (PDA). Digital subtraction of the mfERGs recorded after the drugs were administered from those recorded before was used to extract the components that were eliminated by these drugs. Eight agematched, wild-type (WT) rabbits were studied with the same protocol.


RESULTS
There was no reduction in the amplitude of the cone photoreceptor response of the mfERGs in Tg rabbits. Both the first positive and the first negative waves of the ON-bipolar cell responses were significantly larger in the Tg than in the WT rabbits. Late negative waves of the ON-bipolar cell response were recorded only in the WT rabbits. The first negative wave of the inner retinal responses was larger in the Tg than in the Wt rabbits. The late positive waves were seen mainly in the WT rabbits.


CONCLUSIONS
The ON-bipolar cell and inner retinal responses were altered at the early stage of photoreceptor degeneration in Tg rabbits despite the preservation of the cone photoreceptor responses.
Department of Ophthalmology, Iwate Medical University School of Medicine, Morioka, Iwate, Japan.
Daisuke
D
Yokoyama
Shigeki
S
Machida
Mineo
M
Kondo
Hiroko
H
Terasaki
Tomoharu
T
Nishimura
Daijiro
D
Kurosaka
D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D030801:Animals, Genetically Modified; D004596:Electroretinography / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000494:pharmacology; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology*; D010875:Pipecolic Acids / Q000494:pharmacology; D017354:Point Mutation; D011817:Rabbits; D051245:Retinal Bipolar Cells / Q000502:physiology; D012162:Retinal Degeneration / Q000235:genetics / Q000503:physiopathology*; D012243:Rhodopsin / Q000235:genetics*; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
D000613:Aminobutyrates; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D010875:Pipecolic Acids; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; C029262:2,3-piperidinedicarboxylic acid; D016202:N-Methylaspartate; D012243:Rhodopsin; C012729:2-amino-4-phosphonobutyric acid