ERG and Behavioral CFF in Light-Damaged Albino Rats.

The full-field ERG is useful for index rod- or cone-mediated retinal function in rodent models of retinal degeneration. However, the relationship between the ERG response amplitudes and visually guided behavior, such as flicker detection, is not well understood. A comparison of ERG to behavioral responses in a light-damage model of retinal degeneration allows us to better understand the functional implications of electrophysiological changes. Flicker-ERG and behavioral responses to flicker were used to determine critical flicker frequency (CFF) under scotopic and photopic conditions before and up to 90 d after a 10-day period of low-intensity light damage. Dark- and light-adapted ERG flash responses were significantly reduced after light damage. The a-wave was permanently reduced, while the b-wave amplitude recovered over three weeks after light damage. There was a small, but significant dip in scotopic ERG CFF. Photopic behavioral CFF was slightly lower following light damage. The recovery of the b-wave amplitude and flicker sensitivity demonstrates the plasticity of retinal circuits following photopic injury.

Age-related changes in Cngb1-X1 knockout mice: prolonged cone survival.

The rod photoreceptor cGMP-gated cation channel has an essential role in phototransduction functioning as the primary point for calcium and sodium entry into the rod outer segment. The channel consists of two subunits, α and ß. The α-subunit can function in isolation as an ion channel, and the ß-subunit modulates channel activity and has a structural role. We previously reported that a mouse knockout (KO) of the ß-subunit and related glutamic acid-rich proteins (GARPs) attenuates rod function and causes structural alterations and slowly progressive retinal degeneration. Here, we have extended our functional analyses of the KO mice evaluating rod and cone function using the electroretinogram in mice up to 4 months of age. Retinal stratification is preserved in the knockout mice at 3 months, and a significant number of cones remain up to 7 months based on PNA staining of cone sheaths. Electroretinography of KO mice at 1 month old revealed a diminished dark-adapted b-wave and normal light-adapted b-wave compared to wild-type mice. Over the next 3 months, both dark- and light-adapted b-wave amplitudes declined, but the reduction was greater for dark-adapted b-wave amplitudes. In one-month-old mice, the critical flicker frequency (CFF) was substantially lower for the KO mice at scotopic intensities, but normal at photopic intensities. CFF values remained stable in the KO mice as the b-wave amplitudes decreased with age. Declining b-wave amplitudes confirm an RP phenotype of rod followed by cone degeneration. Flicker responses show that the cone circuits function normally at threshold despite significant losses in the maximum light-adapted b-wave amplitude. These results confirm that rods are marginally functional in the absence of the ß-subunit and in addition show that CFF may be a more sensitive measure of remaining functional cone vision in animal models of RP undergoing progressive rod-cone degeneration.

Flicker assessment of rod and cone function in a model of retinal degeneration.

Critical flicker frequency (CFF) is the lowest frequency for which a flickering light is indistinguishable from a non-flickering light of the same mean luminance. CFF is related to light intensity, with cone photoreceptors capable of achieving higher CFF than rods. A contemporaneous measure of rod and cone function can facilitate characterization of a retinal degeneration. We used sinusoidal flicker ERG to obtain CFF values, over a wide range of light intensities, in RCS dystrophic (RCS-p(+)) and wild type rats. Recordings were made at PN23, PN44, and PN64. The CFF curve in control animals increased in proportion to the log of stimulus intensity, with a gentle slope over the lowest 4 log-unit intensity range. The slope of the CFF curve dramatically increased for higher intensities, indicating a rod-cone break. In the RCS rats the rod driven CFF was significantly lower in amplitude compared to normal rats at the earliest age tested (PN23). By PN64 the rod driven CFF was immeasurable in the RCS rats. The amplitude of the cone driven CFF approached normal values at PN23, but was greatly reduced by PN44. By PN64 the entire CFF function was greatly depressed and there was no longer a discernable rod-cone break. These CFF/ERG data show that RCS rats exhibit significant early degeneration of the rods, followed soon after by degeneration of the cones. Using this approach, rod and cone function can be independently accessed using flicker ERG by testing at a few select intensities.