The third–order neuron response contributes to shaping the negative type electroretinogram (ERG) in sodium iodate–treated rats

Abstract

Abstract: : Purpose: Negative type ERGs are occasionally seen in retinitis pigmentosa (RP) (Cideciyan et al., 1993). We investigated a possible mechanism of shaping negative ERG in animal models with photoreceptor degeneration. Methods: Sprague–Dawley rats (n=25) were intravenously injected with 60mg/kg of sodium iodate (NaIO₃) to produce photoreceptor degeneration. Full–field ERGs were recorded under dark adaptation with a maximum stimulus intensity of 2.23 log cd–s/m² at the 7th and 14th days following the administration of NaIO₃. At each time point DL–2–amino–4–phosphonobutyric acid (APB, 1mM) or N–methyl–DL–aspartic acid (NMA, 5 mM) was injected into the vitreous cavity to suppress synaptic transmissions between photoreceptors and second–order neurons or between second– and third–order neurons, respectively. Subsequently, by using a digital subtraction method, we isolated the photoreceptor, 2nd and 3rd–order neuron responses from the waveform recorded before NMA and APB injections. Results:The ERG presented a negative type at the 7th day following the injection of NaIO₃. As a negative wave, the amplitude of the 3rd–order neuron response (100±27.7 µV) was more predominant than that of the photoreceptor response (24.5±4.90 µV). This suggested that the 3rd–order neuron response shaped the leading edge of the a–wave, and is a main constituent of the a–wave in the negative type ERG. At the 14th day, the waveform showed a subnormal type. Although the amplitudes of the photoreceptor and 2nd–order neuron responses remained unchanged, the amplitude of the 3rd–order neuron response was significantly reduced compared to that recorded at the 7th day (p<0.05). The reduction of the 3rd–order neuron response contributed to the waveform change from the negative type to the subnormal type. Conclusions: NaIO₃–injection produced the negative ERG in which the 3rd–order neuron response mainly constituted the a–wave. This could raise a possibility that the 3rd–order neuron response may contribute to shaping the negative ERG in eyes with RP.

Keywords: electroretinography: non–clinical • photoreceptors • retinal pigment epithelium