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C. E. Frederick, S. Weng, D. M. Berson; Arrestin and Response Termination in Ganglion-cell Photoreceptors. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5032.
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© ARVO (1962-2015); The Authors (2016-present)
In intrinsically photosensitive retinal ganglion cells (ipRGCs), the photopigment melanopsin drives a signaling cascade like that in invertebrate photoreceptors. Arrestins presumably contribute to termination of the ipRGC cascade at light offset, but this is not certain. Based on homology with the arrestins operating in invertebrate phototransduction, we hypothesize that arrestin-2 (β arr-1) or arrestin-3 (β arr-2) might be involved in this process.
We analyzed expression of rod arrestin (arr-1), cone arrestin (arr-4), arrestin-2 and arrestin-3 in melanopsin-expressing ganglion cells by 1) double immunofluorescence in vertical sections of rat and mouse retina and 2) single-cell RT-PCR in rat ipRGCs retrolabeled from the suprachiasmatic nucleus, harvested from primary culture, and shown to contain melanopsin transcripts. The kinetics of response termination were evaluated in ipRGCs by multielectrode array (MEA) recording in retinal wholemounts from arrestin-3 null mice and congenic, age-matched (4-week old) controls. Glutamatergic blockade ensured that all light-driven activity was attributable to melanopsin-based phototransduction. Post-stimulus persistence of spike discharge was compared between the two genotypes.
Neither rod nor cone arrestin were detectable in ipRGCs by immunofluorescence; the absence of cone arrestin expression was confirmed by RT-PCR. Both arrestin-2 and arrestin-3 were detected in melanopsin-expressing ganglion cells at both the mRNA and protein levels. However, in preliminary MEA data, the termination of the light response was not markedly slower in arrestin-3 null mice than in wildtype controls.
Our data exclude rod and cone arrestins as key players in ipRGC response termination. Both arrestin-2 (β arr-1) and arrestin-3 (β arr-2) are present in ipRGCs and could serve such a role, but arrestin 3 is apparently not essential. Response termination may be mediated by arrestin-2 (alone or in combination with arrestin-3), by an uncharacterized arrestin, or by arrestin-independent mechanisms.
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