Pharmacological Dissection of Laminar Contributions to Intrinsic Optical Signals in the Retina

Abstract

 

Purpose:

 

To investigate the anatomic origins of intrinsic optical signals in the mammalian retina via pharmacological agents targeting specific retinal cell layers.

 

Methods:

 

Adult cats were anesthetized with sodium thiopental, paralyzed with vecuronium bromide and artificially respirated. Using a modified fundus camera, the retina was stimulated with visible (550nm) patterned stimuli and illuminated in the near infrared (700–900nm), while intrinsic optical signals were recorded with a cooled CCD camera. Optical signals were recorded before and after intravitreal injections of Cis–2,3 piperidine dicarboxylic acid (PDA) and L–2–amino–4–phosphonobutyric acid (APB), or tetrodotoxin (TTX) to suppress specific retinal activity. ERG and PERG recordings were analyzed for specific components attributed to particular retinal layers.

 

Results:

 

As previously reported, the intrinsic signals demonstrated a tight spatial correlation with the retinal stimulus location. Immediately after photobleaching of the retina, the retinal intrinsic signals were abolished. Subsequent recovery of the retinal signals tracked closely with the recovery of the ERG. The intrinsic retinal signals were not abolished after intravitreal TTX injections, but remained consistent in amplitude and time course. The effectiveness of the TTX was confirmed by ERG and PERG recordings. Preliminary recordings indicate that the intrinsic retinal signals also persist largely unaltered after intravitreal injections of APB+PDA. ERG recordings after such APD+PDA injections demonstrate the expected suppression of the b– and d–wave components of the ERG.

 

Conclusions:

 

Intravitreal injections of agents that suppress the activity of ganglion cells, ON and OFF bipolar cells and other post–receptor cells failed to abolish or significantly alter the imaged retinal intrinsic signals. These results suggest that a major component of these intrinsic signals arises from the outer retina.  

 

Keywords: retinal connections, networks, circuitry • imaging/image analysis: non-clinical • photoreceptors