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S. Anna Sargsyan, P. Michael Iuvone; Cocaine- and amphetamine-regulated transcript (CART): a novel retinal neuropeptide. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2641.
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Dopamine modulates multiple dimensions of light-adapted vision, including daytime contrast sensitivity, visual acuity, and light-adapted electroretinographic responses (Jackson et al., J Neurosci 2012). CART is highly expressed in the brain, where it functions as a neuropeptide and a modulator of dopamine signaling (Rogge et al., Nature Reviews 2008). The mRNA for CART, Cartpt, is highly expressed in the retina (Douglass et al., J Neurosci 1995), and CART was detected in on-off direction-selective retinal ganglion cells [RGCs (Kay et al., J Neurosci 2011)], other bistratified RGCs (Ivanova et al., JCN 2013), and dopaminergic amacrine cells [DaACs (Gustincich et al., PNAS 2004)]. Yet its function in the retina has not been explored. Our study aimed to characterize the CART-expressing retinal cells and elucidate whether dopamine can affect CART levels.
Immunofluorescence staining for CART and tyrosine hydroxylase was used to identify CART-expressing cells and DaACs, respectively, in retinas of wild type (WT), ThloxP/loxP and Chx10-CreThloxP/loxP [retina-specific dopamine deficiency (Jackson et al., J Neurosci 2012)] mice. ImageJ image analysis software was used to quantify CART levels. Treatment with 10 mg/kg of L-3-4-dihydroxyphenylalanine (L-DOPA) of Chx10-CreThloxP/loxP mice was used to study the effect of restoring retinal dopamine on CART levels. qRT-PCR was used to examine the expression of Cartpt in retinas of WT and dopamine D4 receptor-deficient (Drd4-/-) mice.
CART-like immunoreactivity was detected in DaACs, in another subset of amacrine cells, in previously characterized RGCs, and in the outer segments of photoreceptors. The cells with the highest expression of CART were DaACs. CART levels were significantly reduced in the processes of DaACs of Chx10-CreThloxP/loxP mice when compared to those of ThloxP/loxP control mice. Daily L-DOPA treatment for one week increased CART levels in the processes of DaACs of Chx10-CreThloxP/loxP mice. Retinal Cartpt expression showed diurnal rhythmicity in WT mice, which was significantly altered in Drd4-/- mice.
CART was widely expressed in many cell types in the retina, with its highest expression seen in DaACs. Retinal CART expression was modulated by dopamine. Cartpt expression had diurnal rhythmicity in WT mice, suggesting that its expression was under the control of circadian clock transcription factors.
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