Abstract
Purpose :
To determine the contribution of second- and third-order retinal neurons to the photopic electroretinograms (ERGs) after the degeneration of the rods in rhodopsin P347L transgenic rabbits (Tg).
Methods :
Four wild type rabbits (WT) and four Tg rabbits were studied at 18 months-of-age. The photopic ERGs elicited at stimulus onset and offset were analyzed. To block different retinal pathways, 2-amino-4-phosphonobutyric acid (APB) and 6-cyano-7-nitroquinoxaline-2, 3 (1H,4H)-dione (CNQX), and tetrodotoxin (TTX) and N-methyl-DL-aspartic acid (NMDA) were injected intravitreally. Digital subtraction of the post-drug ERGs from the pre-drug ERGs was used to determine the contributions of the ON-components blocked by APB, the OFF-components blocked by CNQX, and the third-order neurons blocked by TTX+NMDA.
Results :
Contribution of the cone photoreceptors to the photopic ERGs in Tg rabbits was about 10% of that in WT rabbits. The amplitudes of the positive waves of the ON-components at stimulus onset in Tg rabbits were about one-half as large as those in WT. On the other hand, the amplitudes of the positive waves of the OFF-components at stimulus offset in Tg rabbits were about 1.4 to 2.3 times larger than those in WT. Tg rabbits had a positive wave at stimulus offset which was reduced after the TTX+NMDA injection.
Conclusions :
A reduced ON-component and an augmented OFF-component with abnormal responses of the third-order neurons contributed to the cone ERGs after the loss of rod function in Tg rabbits. Our results suggest a complex synaptic remodeling of the residual retinal cells in the advanced stage of Tg rabbits.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.