The Electroretinogram I-Wave, a Component Originating in the Retinal OFF-Pathway, Associates With a Myopia Genetic...

Area of Science:

• Ophthalmology
• Genetics
• Neuroscience

Background:

• Myopia, or nearsightedness, has strong genetic associations, particularly near the GJD2 gene.
• Recent studies linked this genetic locus to cone-driven electroretinograms (ERGs), specifically implicating OFF pathway signals.
• The ERG i-wave is hypothesized to originate from retinal OFF pathways.

Purpose of the Study:

• To investigate the association between the ERG i-wave and the myopia risk locus near the GJD2 gene.
• To test the hypothesis that the ERG i-wave is influenced by genetic variations at this myopia risk locus.

Main Methods:

• Analyzed standard LA3 ERGs using conductive fiber electrodes.
• Examined ERGs from patients with monogenic deficits affecting retinal ON and/or OFF pathways.
• Measured i-wave amplitudes in adult participants from the TwinsUK cohort, blinded to GJD2 genotype, adjusting for covariates.

Main Results:

• The ERG i-wave persisted when ON pathway signals were absent but was abolished if both ON and OFF pathways were impaired.
• In 184 TwinsUK participants, i-wave amplitude was significantly associated with allelic dosage at the GJD2 myopia risk locus (P = 0.027).

Conclusions:

• Patient ERGs support the i-wave originating from cone-driven OFF pathways.
• Significant association between i-wave amplitude and allelic dosage at the GJD2 locus reinforces the role of cone-driven signaling in myopia.
• These findings underscore the relevance of the OFF pathway in the context of the GJD2 myopia risk locus.