Relative Genetic and Environmental Contributions to Variations in Human Retinal Electrical Responses Quantified in a Twin Study

Abstract

PurposeTo estimate heritability of parameters of human retinal electrophysiology and to explore which parameters change with age.DesignProspective, classic twin study.ParticipantsAdult monozygotic and dizygotic twin pairs recruited from the TwinsUK cohort.MethodsElectroretinogram responses were recorded using conductive fiber electrodes in response to stimuli incorporating standards set by the International Society for the Clinical Electrophysiology of Vision. These parameters were extracted; in addition, photopic negative-response (PhNR; originating from retinal ganglion cells) and i-wave components were extracted from responses to the photopic single flash. Parameter values were averaged from both eyes.Main Outcome MeasuresMean values were calculated for the cohort. Correlation coefficients with age were calculated (averaging parameters from both twins from each pair). Coefficients of intrapair correlation were calculated for monozygotic and dizygotic twins. Age-adjusted heritability estimates were derived using standard maximum likelihood structural equation twin modeling.ResultsResponses were recorded from 210 participants in total (59 monozygotic and 46 dizygotic twin pairs). Ninety-three percent were women. Mean age for the cohort was 62.4 years (standard deviation, 11.4 years). In general, response amplitudes correlated negatively, and implicit times positively, with age. Correlations were statistically significant (P < 0.05) and moderate or strong (coefficient, >0.35) for the following parameters: scotopic standard and bright-flash a-wave implicit times, photopic 30-Hz flicker and single-flash b-wave implicit times, and PhNR and i-wave implicit times. Intrapair correlations were higher for monozygotic than dizygotic twins, suggesting important genetic influences. Age-adjusted estimates of heritability were significant for all parameters (except scotopic dim-flash b-wave implicit time), ranging from 0.34 to 0.85. Highest estimates were for photopic single-flash a-wave and b-wave amplitudes (0.84 and 0.85, respectively).ConclusionsThis study explored heritability of retinal electrophysiologic parameters and included measurements reflecting ganglion cell function. Most parameters showed significant heritability, indicating that genetic factors are important, determining up to 85% of the variance in some cone system response parameters. Scotopic responses tended to show lower heritability (possibly relating to greater rod system susceptibility to environmental factors). Future studies can explore the identity of these genetic factors, improving our understanding of how they shape retinal function.

Effect of varying skin surface electrode position on electroretinogram responses recorded using a handheld stimulating and recording system

“…As ERG parameters from both twins of a given pair are highly correlated [14], only one twin from each pair was included for subsequent analysis. As ERG parameters vary with age [14, 15], the two groups were age-matched by ensuring the same numbers of participants in each age decade.…”

“…As ERG parameters vary with age [14, 15], the two groups were age-matched by ensuring the same numbers of participants in each age decade. This resulted in 28 participants per group.…”

Prevalence of electronegative electroretinograms in a healthy adult cohort

“…In this study, we investigated recordings obtained previously from 211 adult participants from the TwinsUK cohort (with ages ranging from 23 to 86 years) who underwent ISCEV standard recording of ERGs. The primary aim at the time of the recordings had been to investigate heritability of response parameters and investigate factors such as correlation with age 12 ; no recordings were excluded on the basis of waveform shape or relative amplitudes of waveform components. We found that, in response to international standard stimuli, no participant Open access had an electronegative waveform.…”

“…Adult participants were recruited from the TwinsUK cohort, 12 which is a registry of largely healthy adult twins, who have volunteered to participate in research studies at St Thomas’ Hospital, London. 13 Participants underwent full-field ERG testing which incorporated the ISCEV standard protocol.…”

“…We analysed ERG waveforms from a largely healthy sample of over 200 adults (aged between 23 and 86 years) in response to ISCEV standard protocols, and additional stimuli. These responses had been recorded prospectively in the TwinsUK cohort for an investigation of heritability of retinal response parameters, 12 and no recordings were excluded on the basis of electronegativity. In the present study, we looked at the distribution of b:a ratios, looking specifically for the presence of electronegative ERGs in the dark-adapted responses.…”