Pharmacological Dissection of the Pattern ERG (PERG): Insight From Using Uniform Fields

Abstract

Purpose: : To determine the retinal pathway origins of the PERG with help of uniform field stimuli.

Methods: : Transient PERGs and uniform field ERGs were recorded from anesthetized macaques before and at least 1 hour after intravitreal injections of l-APB (2-amino-4-phosphonobutyric acid, 1.6-2.0 mM), TTX (tetrodotoxin, 1-2 µM), and PDA (cis-2,3-piperidinedicarboxylic acid, 3.3-3.8 mM) to block ON pathway, Na⁺-dependent spiking activity, and hyperpolarizing 2^nd and all 3^rd order neuron responses. Pharmacologic effects initially were confirmed using ganzfeld flash ERGs. The PERG stimulus was a 1 cy/deg contrast reversing checkerboard. PERG and uniform field stimuli were presented using the same display monitor (contrast: 84%, mean lum.: 55 cd/m², 2 Hz sq wave modulation). The PERG was also simulated by averaging ON and OFF responses to uniform fields.

Results: : The PERG contained an early positive wave P1 (counterpart of P50 in humans) around 50 ms after pattern reversal, and a negative wave N2 (human N95) around 110 ms. ON responses to the uniform field contained a b-wave followed by a photopic negative response (PhNR); OFF responses contained a brief d-wave and a PhNR. Simulated N2 was the average of ON and OFF response PhNRs, and simulated P1 was the average of the early ON and OFF responses including b- and d-waves. Agents that removed (TTX) or nearly removed (> 80% for PDA, N=2) PhNRs in uniform field responses also removed N2 in PERG and simulations. APB removed the ON PhNR. As a result, both PERG N2 and simulated N2 dropped ~50% (SE=9.7% and 5.1%, respectively; N=4). TTX also altered early responses including b- and d-waves, causing a 50% drop in PERG P1 and a 15% drop in simulated P1. APB removed positive ON and enhanced OFF responses, while PDA did the reverse. For both agents, ON response effects were more prominent. Simulated P1 dropped ~60% (SE=6.3%, N=4) after APB whereas P1 became larger after PDA in PERG (123% and 460% of control in two animals) and simulation (150% and 300%).

Conclusions: : APB, TTX and PDA had similar effects on PERG and simulated PERG from ON and OFF responses. Uniform field ERGs improved understanding of the pathway origins of the PERG.

Keywords: retina: proximal (bipolar, amacrine, and ganglion cells) • retinal connections, networks, circuitry