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

Abstract

Purpose: To estimate heritability of parameters of human retinal electrophysiology and to explore which parameters change with age.

Design: Prospective, classic twin study.

Participants: Adult monozygotic and dizygotic twin pairs recruited from the TwinsUK cohort.

Methods: Electroretinogram 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 measures: Mean 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.

Results: Responses 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).

Conclusions: This 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.

Figure 1

Graphs showing example electroretinography responses from a single participant to International Society for the Clinical Electrophysiology of Vision stimuli with labeling of parameters as well as their cellular origin. A, C, E, Averaged responses to white flashes delivered in the dark after 20 minutes of dark adaptation: (A) 0.01 cd s/m². (C) 3.0 cd s/m², and (E) 10.0 cd s/m². B, D, Averaged responses to stimuli delivered after 10 minutes of adaptation to a 30-cd s/m² white background: (B) Response to 30-Hz flicker and (D) response to 3.0-cd s/m² flash. Additional parameters (photopic negative response [PhNR] and i-wave) are labeled in (D). Asterisks denote components whose amplitudes were found to have high heritability as estimated in this study. ^∗Denotes point estimate of heritability of more than 0.75, which was the case for scotopic b-wave amplitudes in response to the brighter flashes. ^∗∗Denotes heritability point estimates of more than 0.80, which was the case for photopic flash a-wave, b-wave, and i-wave amplitudes.

Figure 2

Plots of International Society for the Clinical Electrophysiology of Vision response parameters found to correlate significantly with age. Dashed lines show a simple fit by linear regression. A, Scotopic standard flash a-wave implicit time. B, Scotopic bright flash a-wave implicit time. C, Photopic 30 Hz flicker response peak time. D, Photopic standard flash b-wave implicit time.

Figure 3

Bar graphs showing coefficients of intrapair correlation for monozygotic and dizygotic twins for International Society for the Clinical Electrophysiology of Vision parameters. (A, scotopic stimuli; B, photopic stimuli). In labels to the bars, numbers without units refer to the standard flash intensities in photopic cd s/m². DZ = dizygotic; MZ = monozygotic.

Figure 4

Scatterplots showing (A) photopic negative-response (PhNR) implicit time and (B) i-wave implicit time against age (as derived from the response to the International Society for the Clinical Electrophysiology of Vision standard photopic flash). Dashed lines show a simple fit by linear regression.

Figure 5

Bar graphs showing coefficients of intrapair correlation for parameters relating to the photopic negative response (PhNR) and i-wave for monozygotic (MZ) and dizygotic (DZ) twins (as derived from the response to the International Society for the Clinical Electrophysiology of Vision standard photopic flash).