Melanopsin's Phototransduction and Spiking Response Are Evident in the Photoreceptor-Directed Multifocal Electroretinogram

Existing methods of measuring melanopsin's functional response in humans can only return a measure of a postcortical interpretation of the intrinsic photoresponse. There is physiological ex vivo evidence to suggest that the retinal activity of melanopsin can differ from its cortical interpretation. We developed an in vivo method for isolating the multifocal neuroretinal responses originating from melanopsin signaling in humans (seven males, one female). These electrical responses can be decomposed into three separable components; (1) a very fast positive potential with timing on the scale of melanopsin's phototransduction cascade; (2) a slow and sustained negative-going, depolarization consistent with the inherent spiking response of melanopsin; and (3) a positive potential following the onset of the spiking response that is a candidate for the intraretinal response to melanopsin activation. It was possible to manipulate the duration of the sustained signal component by introducing ambient illumination during the test and thereby, demonstrating in vivo melanopsin's photochemical tristability. A topographical map of the melanopsin electrical response was then created using melanopsin-directed multifocal stimuli, and we show that the amplitude of each waveform component maps strongly with the eccentric cell density of intrinsically photosensitive retinal ganglion cells. We demonstrate the ability of this technique to generalize to any photoreceptor class by mapping the retinal responses of the rod- and cone-directed multifocal electroretinogram and which may find clinical applications in ophthalmic diseases. These findings show that the amplitude, timing, and polarity of the melanopsin response are distinctly unique compared with the rod and cone neuroretinal electrical responses.