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Purpose  The rodent retina does not exhibit a positive OFF-response in the electroretinogram (ERG), which makes it difficult to evaluate its OFF-pathway functions  in vivo . We studied the rod-driven OFF pathway responses by using a dark-adapted 10-Hz flicker ERG procedure in mouse.    Materials and Methods  Conventional ERGs and 10-Hz dark-adapted flicker ERGs were obtained in wild-type mice ( C57BL/6 ), in mice with pure rod ( cpfl1 ) or pure cone ( rho −/−  ) function, and in  nob1  mice which have a selective ON-pathway defect. To isolate the response from ON or OFF pathway, glutamate analogs 2-amino-4-phosphobutyric acid (APB, an ON pathway blocker) and cis-2, 3-piperidine-dicarboxylic acid (PDA, an OFF pathway blocker), were injected intravitreally.    Results  The amplitude-intensity profile of the dark-adapted 10-Hz flicker ERG in the wild-type mice exhibits two peaks at middle and high light intensities. The two peaks represent rod- and cone-driven responses respectively. In APB-treated  C57BL/6  mice and in  nob1  mice, the dark-adapted ERG b-waves were absent. However, both rod- and cone-driven OFF pathway responses were evident with flicker ERG recording. At middle light intensities that activate only rod system, the flicker ERG responses in saline-injected  nob1  mice were similar to those in APB-injected  cpfl1  mice and wild-type mice. These responses are sensitive to PDA. The amplitudes of these rod-driven OFF pathway responses were approximately 20% of the total rod-driven flicker ERG responses.    Conclusion  We demonstrate that the rod-OFF bipolar cell pathway is functional in the outer retina. The dark-adapted flicker ERG is practical for the evaluation of rod- and cone-driven responses, and the residual OFF pathway signals in subjects with ON pathway defects.

Rod-Driven OFF Pathway Responses in the Distal Retina: Dark-Adapted Flicker Electroretinogram in Mouse