Abstract
PurposeThe 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 MethodsConventional 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.ResultsThe 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.ConclusionWe 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.
Highlights
Two traditional rod pathways are known to exist in mammals [1,2,3]
In APB-treated C57BL/6 mice and in nob1 mice, the dark-adapted ERG b-waves were absent. Both rod- and cone-driven OFF pathway responses were evident with flicker ERG recording
We demonstrate that the rod-OFF bipolar cell pathway is functional in the outer retina
Summary
The primary pathway for rod signals is transmission from rods R rod bipolar cells R AII amacrine cells R cone ON and OFF bipolar cells R ganglion cells. Recent studies reveal the existence of a third rod pathway: a direct connection between rods and OFF cone bipolar cells [4,5,6,7,8,9,10]. This rod pathway appears to be a common feature of the mammalian retina [11,12,13,14]. No study has been conducted to investigate the function of this newly discovered OFF pathway in electroretinogram (ERG), an objective and reliable method for evaluating the function of the outer retina in living animal
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