Stimulus-evoked intrinsic optical signals in the retina: pharmacologic dissection reveals outer retinal origins.
OBJECTIVE
To elucidate the anatomic origins of stimulus-evoked intrinsic optical signals in the mammalian retina by using selective pharmacologic blockade of specific retinal layers.


METHODS
Four adult cats were used to investigate the stimulus-evoked intrinsic signals. The retinas were visually stimulated with a liquid crystal display (LCD) integrated into a modified fundus camera. The evoked signals in the near infrared (NIR) were recorded with a digital camera to image the changes in the optical reflectance of the retinas. Variants of the electroretinogram (pattern ERG and long-pulse ERG) were also recorded as additional measures of retinal function. Specific retinal layers were inactivated via intravitreal injections of the voltage-gated sodium channel blocker, tetrodotoxin (TTX), the metabotropic glutamate receptor (mGluR6) agonist, 2-amino-4-phosphonobutyric acid (APB), and/or the ionotropic glutamate receptor antagonist cis-2,3 piperidinedicarboxylic acid (PDA). The stimulus-evoked intrinsic signals were imaged before and after drug injection.


RESULTS
ERG recordings and tests of the consensual pupillary response confirmed the effectiveness of each drug. Yet despite the pharmacologic blockade of the inner retina (TTX) and postreceptoral retinal circuitry (APB and PDA), the stimulus-evoked intrinsic signals remained essentially unaltered from preinjection conditions. Similarly, the time course of the signal did not appreciably shift in time or shape.


CONCLUSIONS
The findings demonstrate that stimulus-evoked intrinsic signals persist after injection of APB, PDA, and TTX, drugs that work to suppress inner and postreceptoral retinal circuitry. The persistence of the intrinsic signals after administration of these drugs indicates that the dominant intrinsic signals are likely to arise from the outer retina.
Schallek
Jesse
J
Department of Neurosurgery, SUNY Upstate Medical University, Syracuse, New York 13210, USA.
Kardon
Randy
R
Kwon
Young
Y
Abramoff
Michael
M
Soliz
Peter
P
Ts'o
Daniel
D
D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D002415:Cats; D004594:Electrophysiology; D004596:Electroretinography; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007259:Infrared Rays; D007267:Injections; D010775:Photic Stimulation; D010875:Pipecolic Acids / Q000494:pharmacology; D051245:Retinal Bipolar Cells / Q000187:drug effects; D012165:Retinal Ganglion Cells / Q000187:drug effects; D055211:Retinal Photoreceptor Cell Inner Segment / Q000187:drug effects; D055214:Retinal Photoreceptor Cell Outer Segment / Q000502:physiology* / Q000528:radiation effects; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014822:Vitreous Body
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; C012729:2-amino-4-phosphonobutyric acid