ON and OFF Electroretinography and Contrast Sensitivity in Duchenne Muscular Dystrophy

Abstract

This study suggests that there are ON and OFF ERG alterations when both rods and cones contribute to the ERG responses in DMD patients. When only cones are activated there is an asymmetrical ERG alteration, also revealed by the contrast sensitivity measurements.

Asymmetrical Functional Deficits of ON and OFF Retinal Processing in the mdx3Cv Mouse Model of Duchenne Muscular Dystrophy

“…The third protocol involved luminance modulation with sawtooth temporal profiles at 4 Hz: ''rapid-on'' for incremental (ON-) and ''rapid-off'' for decremental (OFF-) responses 22,28 under mesopic conditions (preadapted to 1 phot cd/m 2 mean luminance for 5 minutes, 100% temporal luminance contrast). This allowed us to obtain separate ON-and OFF-driven responses, as the total response times were prolonged relative to photopic conditions (see protocol 6 [29][30][31][32] ).…”

“…The mouse mesopic ON-response presented here is similar to the human response. 22,43 It is composed of a very small first negative trough (N ON ), a positive peak (P ON~6 9 ms post onset), and a late negativity (LN OÑ 187 ms). The mesopic OFF-response in comparison has an initial slow negativity that reaches a maximum of approximately 85 ms after stimulus onset (N OFF ).…”

“…In that respect, Green et al 18 proposed hypothetical scenarios involving presynaptic changes (e.g., to rod photoreceptor glutamate release) and/or postsynaptic ON-bipolar cell changes (e.g., to binding mechanisms, concentration of indigenous glutamate, affinity and release rate of the postsynaptic binding site, and other modulatory proteins that respond to glutamate release) that could result in the b-wave amplitude and timing manifestations. However, since the effect of APB on photopic ERGs was not examined in these mice, it is unknown if the abnormal ON hypersensitivity is localized to the rod-mediated pathway.Photopic ON/OFF ERG studies in patients and female carriers (i.e., long-flash ERGs, 19-21 sawtooth flicker ERGs, and psychophysical contrast sensitivity measurements 22 ) give reason to suspect that the cone ON-pathway is also selectively altered. Interestingly, however, dysfunctions in both ON-and OFF-responses were revealed under mesopic conditions.…”

“…Interestingly, however, dysfunctions in both ON-and OFF-responses were revealed under mesopic conditions. 22 In the mdx 3Cv mouse, whether ON-and OFF-responses are differentially affected (e.g., Green et al 18 examined only with an ON-pathway blocker 18 ) and what role the state of adaptation plays have yet to be determined.It is the purpose of the present study to compare scotopic, mesopic, and photopic ERGs using various stimulus modalities that allow the comparison of rod-and mixed rod/cone-versus cone-mediated responses; ON-versus OFF-mediated mechanisms; and outer versus inner retinal processing in wild-type and mdx 3Cv mice. This will provide further insights into the fundamental pathogenetic mechanisms that underlie retinal changes in DMD, as well as reveal whether further parallels exist between the mdx 3Cv mouse model and DMD in humans.…”

Ocular and neurodevelopmental features of Duchenne muscular dystrophy: a signature of dystrophin function in the central nervous system

“…[16][17][18][19][20] Recently, Dp427, Dp260 and Dp140 expressions have been identified in inner retinal layer neurons as well; Dp427 was expressed proportionately more at cone than rod synapses, in bipolar cells and some amacrine cells. 19 Mutations downstream of exon 30, which affect Dp260 expression, are associated with an abnormal scotopic electroretinogram (ERG) waveform [21][22][23][24] and some impairment of red-green colour vision. 25 In light of the recent retinal expression studies, we sought to explore the clinical ERG as a potential biomarker of CNS dystrophin expression associated with different DMD genotypes and recorded ERGs to a wide range of flash strengths in a cohort of individuals with a range of mutations across the DMD gene.…”