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Polina Lyuboslavsky, Curran Sidhu, Jana T Sellers, Li He, P. Michael Iuvone; Cocaine- and amphetamine-regulated transcript (CART) regulates retinal dopamine and modulates visual function in mice. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
CART is a neuropeptide expressed abundantly in the brain, where it functions as a neuromodulator of dopamine signaling. CART is expressed in the retina in dopamine amacrine cells and bistratified ganglion cells, and CART expression is regulated in part by retinal dopamine (Sargsyan & Iuvone, ARVO E-Abstract 2641, 2014). However, the function of CART in retina has not been explored. This study was conducted to determine how removal of CART affects visual function.
Cartpt -/- (CART KO; Asnicar et al., Endocrinol. 2001;142(10):4394-400) mice and wild type (WT) C57BL/6J mice were used in our experiments. The levels of dopamine and its metabolite DOPAC were measured in CART KO and WT mice using HPLC. Contrast sensitivity was measured in CART KO and WT mice using optokinetic tracking (OKT) at a spatial frequency 0.64 (c/d). CART KO and WT mice were treated daily with intraperitoneal injections of 10 mg/kg L-DOPA in 0.1% ascorbic acid; on the 8th day of treatment, contrast sensitivity was measured. Injection of L-DOPA continued and dark-adapted and light-adapted ERG recordings were performed on days 10 and 11 of treatment. Spectral-domain optical coherence tomography (SD-OCT) measurements were taken for CART KO and WT mice. Tyrosine hydroxylase (TH) mRNA and protein levels were measured by qRT-PCR and Western blot analyses, respectively.
Retinal DOPAC and dopamine levels were significantly reduced in the CART KO mice when compared to those in WT mice (p<0.001), as were TH mRNA (p=0.007) and protein (p = 0.041). Visual contrast sensitivity (p<0.001) and scotopic and photopic ERG b-wave amplitudes (p<0.001) were lower in CART KO mice than in WT controls. Daily L-DOPA treatment significantly improved contrast sensitivity (p<0.001) and photopic and scotopic ERG b-wave amplitudes (p<0.001) in CART KO mice. SD-OCT measurements found significant decreases (P<0.001) in photoreceptor layer thickness and in total retina thickness in CART KO mice compared to WT mice.
CART neuropeptide regulates retinal dopamine synthesis and metabolism in the retina. Lack of CART peptide leads to reduced retinal light responses and impaired visual function.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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