The Effect of intravitreal N-methyl-DL-aspartic acid on the electroretinogram in Royal College of surgeons rats

Abstract

Purpose: To investigate how the third-order neuronal response contributes to shaping the electroretinogram (ERG) in the Royal College of Surgeons (RCS) rat.

Methods: Full-field ERGs were recorded from dystrophic RCS rats (n = 30) at 4, 6, 8, 10, 12, or 14 weeks of age in response to different stimulus intensities (maximum intensity, 0.84 log cd-s/m(2)). N-methyl-DL: -aspartic acid (NMDA, 5 mM) was injected into the vitreous cavity of the right eyes to eliminate the third-order neuronal response. The left eyes received the vehicle and served as controls. The third-order neuronal response was isolated by digitally subtracting waveforms of the NMDA-injected eyes from those of the control eyes.

Results: The ERG a- and b-waves deteriorated with the age of the rat. The third-order neuronal response was preserved to a greater degree than the b-wave despite progression of photoreceptor degeneration. Intravitreal injection of NMDA attenuated the a-wave and enhanced the b-wave across the stimulus range from low to middle intensities. This tendency became more pronounced with advancing rat age. In aged dystrophic RCS rats this phenomenon was seen even at maximum intensity. The difference between NMDA-injected and vehicle-injected eyes was larger for the threshold than for the maximum amplitude at each examined time point (P < 0.001). Intravitreal injection of NMDA decreased implicit times of the a- and b-waves after the rats reached 8 weeks of age (P < 0.005 for the a-wave).

Conclusion: With advancing photoreceptor degeneration, the third-order neuronal response made a greater contribution to shaping the a- and b-waves in dystrophic RCS rats.