Third‐Order Neuronal Responses Contribute to Shaping the Negative Electroretinogram in Sodium Iodate–Treated Rats

Abstract

Purpose: To determine possible mechanisms that shape the negative electroretinograms (ERGs) in rats with photoreceptor degeneration induced by destruction of the retinal pigment epithelium. Methods: Sprague-Dawley rats (n = 48) were injected intravenously with 60 mg/kg of sodium iodate (NaIO3). Full-field ERGs were elicited by different stimulus intensities with a maximum luminance of 1.23 log cd-s/m2 and recorded at 6 hr and on days 7, 14, and 28 after the NaIO3 injections. DL-2-amino-4-phosphonobutyric acid (APB, 1 mM) or N-methyl-L-aspartic acid (NMDA, 5 mM) was injected into the vitreous cavity to isolate photoreceptor (PIII), second-order, and third-order neuronal responses. After recording the ERGs, animals were sacrificed for histological analysis. Results: Negative ERGs were recorded under scotopic conditions on day 7 after the NaIO3 injection. An intravitreal injection of NMDA eliminated most of the a-wave, resulting in the abolition of the negative ERG. On days 14 and 28, the a-wave amplitudes were reduced compared to those on day 7 with the loss of the negative ERGs. The mean amplitudes of the PIII and second-order neuronal responses were progressively reduced until day 7. In contrast, the mean amplitude of the third-order neuronal responses were relatively well-preserved until day 7 and then were decreased between days 7 and 14. As a result, the amplitude of the third-order neuronal response dominated over the second-order neuronal response on day 7. There was no significant difference in the middle and inner retinal morphology at each time point. Conclusions: NaIO3 produced negative ERGs transiently, and the third-order neuronal responses were the main contributors to the negative ERG. The relative preservation of the third-order neuronal response plays a role in shaping the negative ERGs in this model.