Differentiating between Ischemic and Non-Ischemic Origins of the “Negative” Electroretinogram

Abstract

 

Purpose

 

Strong attenuation of the electroretinographic (ERG) b-wave in the presence of a normal or less reduced a-wave (‘negative ERG’) is typically caused either by defects in synaptic transmission between photoreceptors and ON-bipolar cells or by ischemia of the inner retina. The purpose of this study was to explore whether ERG flicker responses permit discrimination of synaptic and ischemic cases.

 

Methods

 

Three murine models of ophthalmic disease demonstrating negative ERG, the nob1 mouse model of congenital stationary night blindness characterized by deficits in the ON-pathway, the oxygen-induced retinopathy rat model of retinopathy of prematurity (‘ROP rat’) characterized by inner retinal ischemia, and the Rs1h^y/- mouse model of X-linked juvenile retinoschisis, were studied. After a dark-adapted single-flash ERG intensity series (-4 to 1.5 log cd s/m²), a flicker ERG frequency series (12 steps from 0.5 to 30 Hz) at the International Society for Clinical Electrophysiology of Vision standard flash (ISCEV SF) intensity (0.5 log cd s/m²) was performed. This series was considered in three frequency ranges that are dominated by activity in the A) rod system (<5 Hz), B) cone ON-pathway (5-15 Hz), and C) cone OFF-pathway (>15 Hz).

 

Results

 

In ROP rats, photoreceptors are supplied by the choroid but both ON- and OFF-bipolar cells are ischemic due to loss of retinal vasculature; correspondingly, ROP rats had nearly normal a-waves but reduced flicker responses in all ranges (A-C). nob1 mice likewise have normal photoreceptor function and, thus, a-waves were not reduced. As only the ON-pathway is defective in nob1 mice, flicker signals were reduced in ranges A and B but not C. In Rs1h^y/- mice, there are patchy alterations in both the photoreceptor and bipolar cell layers, but not in the same vertical column. Consequently, the fraction of functional photoreceptors is larger than that of functional bipolar cells receiving photoreceptor signals. Therefore, there was a noticeably reduced a-wave, an even more reduced b-wave, and attenuated flicker responses in all ranges (A-C).

 

Conclusions

 

The response to flickering ISCEV SF light at specified frequencies can be compared to the size of the a-wave to discriminate the pathophysiology of the negative ERG, including synaptic and ischemic conditions.

 

Keywords: 510 electroretinography: non-clinical • 689 retina: distal (photoreceptors, horizontal cells, bipolar cells)