The frequency-response electroretinogram distinguishes cone and abnormal rod function in rd12 mice

Area of Science:

• Ophthalmology
• Neuroscience
• Genetics

Background:

• Early studies suggested cone function was responsible for residual vision in Rpe65 knockout mice.
• This notion has been increasingly challenged, particularly concerning rd12 mice, an animal model for RPE65 Leber congenital amaurosis.
• Electroretinograms (ERGs) in rd12 mice show delayed photopic responses, complicating interpretation and resembling rod function.

Purpose of the Study:

• To investigate the source of residual vision in rd12 mice.
• To compare frequency-response ERGs in mice with normal, pure rod, and pure cone function against rd12 mice.
• To establish frequency-response ERGs as a method to distinguish rod- and cone-driven retinal responses.

Main Methods:

• Comparative analysis of flicker ERGs across different mouse models (C57BL/6J, cpfl5, Rho(-/-), and rd12).
• Evaluation of responses under varying adaptation levels and stimulus intensities.
• Utilizing frequency-response characteristics (5-35 Hz) to differentiate rod and cone contributions.

Main Results:

• Normal rods respond to low-frequency flicker (5, 15 Hz); normal cones respond to both low and high frequencies (5-35 Hz).
• rd12 mice exhibited responses to low-frequency flicker (5, 15 Hz) but not high-frequency flicker (25, 35 Hz), similar to pure rod function models.
• Double mutant rd12 mice confirmed that abnormal rods are the source of residual vision.

Conclusions:

• Residual vision in rd12 mice is primarily mediated by abnormal rod function.
• Frequency-response ERGs provide a reliable method for distinguishing between rod- and cone-driven visual responses in rd12 mice.
• This technique offers a valuable tool for assessing the functional contributions of retinal rods and cones.